FOR OLDER BLACK MEN, A LIFESAVING PUSH FOR MORE PROSTATE CANCER TESTS

By Justin Wm. Moyer / The Washington Post

Posted Feb 3, 2019 at 10:35 AM Updated Feb 3, 2019 at 10:35 AM

WASHINGTON — African-American men are more likely than white men to develop and die of prostate cancer, and there is a debate about when they should be tested.

For Navin Shah and Vladimir Ioffe, a urologist and a radiation oncologist, respectively, in Prince George’s County, conversations between patients and doctors might not be enough to prevent illness. Sixty percent of their patients are African-American, and they recommend that every black man older than 50 be screened, while the federal government recommends only that the prostate test known as PSA screening be discussed with patients.

“I think we are not doing justice to African Americans if we do not screen them,” Shah said. “It is a very sad story.”

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Shah and Ioffe have data to support PSA screening in a recently published paper for Urology Times. Looking at tissue from nearly 2,900 biopsies, they found that after the U.S. Preventive Services Task Force — the federal agency that weighs in on the need for the tests — said routine screening was unnecessary in 2012, fewer biopsies were performed. But more of those biopsies revealed cancer, suggesting that some cases are being diagnosed later than they could have been.

“Despite a reduction in the total number of prostate biopsies by 30 percent, there was a 100 percent increase in the total number of positive prostate biopsies,” the study says — because, as Ioffe put it, when “men are not being screened, their cancer is progressing.”

“The main point of this whole thing is trying to advocate for high-risk men,” Ioffe said. “They need to be screened. Primary-care doctors shouldn’t be confused by the current recommendations.”

Discussing the need for PSA tests can set physicians against epidemiologists — or “number-crunchers,” as Ioffe called them. On one hand, prostate cancer doesn’t always kill. Testing every man could lead to a lot of unnecessary treatment — including invasive steps such as prostatectomy that can lead to side effects such as incontinence or erectile dysfunction.

According to this interpretation, Shah and Ioffe’s finding that fewer biopsies are being conducted is a good sign, and a higher proportion of biopsies showing cancer means that healthy men aren’t getting unnecessary tests.

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According to the National Institutes of Health, African-American men have a 15 percent chance of getting prostate cancer compared with white men’s 10 percent chance. Black men’s chance of dying is also higher — 4 percent among black men compared with 2 percent among white men.

Last month, researchers at the University of California-San Francisco studying 10,000 African-American prostate-cancer patients found that even those considered low-risk were twice as likely to die as patients in other demographic groups. The median age of black patients was also younger: 62 compared with 65.

William Powell, 63, was a few years into his retirement from the Social Security Administration when he was diagnosed with prostate cancer in 2016.

“I almost had a mental breakdown,” he said. “It was scary. Really, really scary.”

Powell, one of Ioffe’s patients, called his diagnosis and subsequent radiation treatment “an education.” One in four black men like him gets prostate cancer, he learned; many “don’t seek medical attention like they should.”

After his radiation treatment wrapped up last year, his count of prostate specific antigens, an indicator of cancer, is back to normal. Now, he is studying to become a minister and wants to use the pulpit to bring discussions about prostate cancer into the light. The disease is “kind of like a secret” in the black community, he said.

“People need to take this very seriously,” he said. “They really do. It will kill you.”

The U.S. Preventive Services Task Force guidelines, published in the Journal of the American Medical Association in May, say studying prostate cancer among black men should be a “national priority,” but the group was “not able to make a separate, specific recommendation on PSA-based screening.”

“Although it is possible that screening may offer greater benefits for African-American men compared with the general population, currently no direct evidence demonstrates whether this is true,” the guidelines said.

Alex Krist, the task force’s vice chair, said doctors don’t yet know which men with high PSA levels are truly at risk of dying of prostate cancer. If all black men are screened, there will be false positives and overtreatment, and black men — already underrepresented in data that the recommendations are based on — will suffer the consequences.

“We need to be thinking about both the benefits and the harms,” he said. “Maybe it’s not right to screen all African Americans.”″

Ioffe called the guidelines “ambivalent and lukewarm.”

“It means that as far as the task force is concerned, you can either screen or not,” he said. “In contrast to this, we are saying that screening should be clearly recommended and endorsed for high-risk men.”

Daniel J. George, an oncologist at Duke University who reviewed Shah and Ioffe’s paper, said worries about overtreatment are understandable. But he said the paper, while preliminary four years after the task force’s policy change, showed that such concerns were “not a reason not to screen.”

“We may be diagnosing patients later in their disease course,” he said. “That’s the concern I would have with a less-aggressive cancer-screening policy.”

Shah, meanwhile, said the task force’s recommendations weren’t enough. Everybody has a right to know their diagnosis, he said.

“Black people are suffering,” he said. “That’s a fact.”

https://www.dispatch.com/news/20190203/for-older-black-men-lifesaving-push-for-more-prostate-cancer-tests

IMMUNO-ONCOLOGY SUFFERED A SETBACK IN 2018. What’s Next? Checkpoint inhibitors remain top sellers, but it wasn’t all rosy news this year.

Shannon Jones

Todd Campbell

Dec 18, 2018 

PD-1 checkpoint inhibitors are among the most successful and widely used cancer drugs in the world, but they’re not perfect medicines. Many people fail to respond to them or relapse after taking them, so studies have begun that team next-generation drugs with them to try to improve results. Unfortunately, optimism for combination approaches was dealt a big blow in 2018 when Incyte‘s ( HYPERLINK “https://www.fool.com/quote/nasdaq/incyte/incy” NASDAQ:INCY) trial of its IDO inhibitor alongside PD-1s failed.

In this clip from The Motley Fool’s  HYPERLINK “https://www.fool.com/podcasts/industry-focus/” Industry Focus: Healthcare, analyst Shannon Jones and Todd Campbell review the performance of PD-1s in 2018 and offer up thoughts on their future.

A full transcript follows the video.

This video was recorded on Dec. 12, 2018.

Shannon Jones: We’re going to talk about the leaders of the immuno-oncology front, specifically leaders who are producing a kind of drug called checkpoint inhibitors. These PD-1s continue to dominate, but as you describe it, Todd, there have been cracks in the armor. The next key is combination therapies. How do you get them working together?

Todd Campbell: Right. Immuno-oncology has been the big story of this decade. The launch of PD-1 drugs, Bristol Myers‘ Opdivo, Merck‘s Keytruda, they’ve revolutionized how we attack certain cancers like melanoma and lung cancer. But, now that they’re being so widely used, we are starting to see that people do relapse after receiving these therapies, some people don’t respond to them, maybe there are more side effects than we initially thought to their use. So, you’ve got a bunch of different companies who’ve gone out and said, “How can we improve upon these PD-1 drugs?” So, they’re running combination trial therapies, where they’re taking their drugs in development and using them alongside Opdivo and Keytruda and some of these others in that same class of drugs.

The hope had been that that would be a slam dunk. You take these drugs, they have mechanism of action X, you match them up with the anti-PD-1s that have mechanism of action Y, and sure enough, it all works perfectly. More people ended up responding for longer periods.

Unfortunately, some of that enthusiasm got tempered earlier this year. That was because Incyte had been doing a combination study matching up its IDO inhibitor with a PD-1 inhibitor, and unfortunately, when the trial results came in, that combo failed to outperform PD-1 use alone. That really threw a big monkey wrench in the concept of, will combination therapies actually improve upon the therapy or not?

Jones: Todd, I would dare say that that Phase III trial failure with Incyte’s drug was probably the biggest pipeline failure, just because there was so much hype leading into that Phase III readout. Everyone said, “OK, these checkpoint inhibitors, we know that they work in some patients, and for those that do, you see some impressive results. But if we can start to combine with an IDO inhibitor… ” There are other combinations that have been tested and haven’t really proven them out. But, there was so much hype leading into this Phase III study. I think this was probably the biggest heartbreak for many of us that love this space. Yeah, a lot of chip in the armor when it comes to PD-1s. Definitely something to keep an eye on. Some of the hype related to these combination therapies has been tempered moving into 2018, and it’ll probably continue to be so for 2019, as well.

Campbell: I mean, there are 1,500 clinical trials still ongoing for combination therapies with PD-1s. 1,500. Which is crazy. It’s up from 216 in 2016. PD-1s are going to remain the mainstay. If you look at Opdivo and Keytruda, the two top-selling ones, if you combine their sales together, they did almost $4 billion in sales last quarter. If you look at estimates, PD-1s could be $30 billion drugs by 2025. I think PD-1s will remain a mainstay, but for investors heading into 2019, reign in a little bit of your optimism for any trial readouts that are combination-oriented.

https://www.fool.com/investing/2018/12/18/immuno-oncology-suffered-a-setback-in-2018-whats-n.aspx

IDENTIFYING THE RISK FACTORS FOR PROSTATE CANCER AND HOW NEW DEVELOPMENTS MAY HELP

by Daniel Dupuis

There are a number of risk factors of varying severity that can increase or decrease the odds that a man may contract prostate cancer. Recent efforts and initiatives, however, may help provide guidance and resources to help reduce the incidence of prostate cancer and work toward more effective treatment options. There are some substantial developments that may offer very effective treatment options and may even offer solutions that can mitigate the horrific side effects that are inherent to almost all cancer therapies. 

Prostate Cancer Risk Factors

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, for example a person’s age or family history certainly cannot be changed, while others, such as diet can be modified. 

But having a risk factor, or even several, does not mean that you will get the disease. Many people with one or more risk factors never get cancer, while others who get cancer may have no evident risk factors.

One key observation, however, is that a more rigorous testing regimen should be followed if one has more than a few risk factors.

Age

Prostate cancer is rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50. About 6 in 10 cases of prostate cancer are found in men older than 65.

No one can make themselves younger, but the need for more frequent testing increases every year. Additionally, if one is aware that they have elevated risk factors it would be wise to be tested on an annual basis.

New Developments

A new screening tool for prostate cancer has been shown to offer better accuracy than the test currently used by most physicians in the United States. The new test, called the 4Kscore™ test (OPKO Lab), offers various advantages over the more commonly used prostate specific antigen (PSA) blood test.

The new test improves on these common issues with the PSA blood test:

Isn’t specific to cancer; detects a variety of prostate issues

Doesn’t account for a natural tendency for PSA levels to rise with age

The current method for measuring PSA levels has led to a number of false positives in a number of men, which has led them to undergo unnecessary biopsies. The U.S. Preventive Service Task Force gave PSA screening a grade of D in 2012. They said the harm it brings outweighs the benefits.

The new 4Kscore™ test does not replace the current PSA test, but is a follow-up to a positive PSA. It can reduce biopsies, that are uncomfortable and may lead to infection, by 30 to 50%.

Race/Ethnicity

Prostate cancer occurs more often in African-American men and in Caribbean men of African ancestry than in men of other races. African-American men are also more than twice as likely to die of prostate cancer as white men. Prostate cancer occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. The reasons for these racial and ethnic differences are not clear.

This does not mean that Asian-Americans or Hispanics/Latino or Caucasian men should consider foregoing testing; it simply means that African Americans need to maintain a more rigorous testing regimen.

A New Study for African American Men

There has been a recent launch of an initiative that will try to ascertain why African American men are more likely to get, and die, from prostate cancer. It will be the largest study of its kind. It is backed by the National Cancer Institute and aims to enroll 10,000 study subjects. There is, of course, no cost to the participants; in fact, they will all receive a nominal payment of $50. 

Simply search for “RESPOND study and prostate cancer.” 

Family history

Prostate cancer seems to run in families, which suggests that in some cases there may be an inherited or genetic marker that may be categorized as a risk factor. Having a father or brother with prostate cancer more than doubles a man’s risk of developing this disease. (The risk is higher for men who have a brother with the disease than for those who have a father with it.) The risk is much higher for men with several affected relatives, particularly if their relatives were young when the cancer was found.

This simply means that individuals that fit this profile should have more frequent testing.

Diet

The exact role of diet in prostate cancer is not clear, but several factors have been studied.

Men who eat a lot of red meat or high-fat dairy products appear to have a slightly higher chance of getting prostate cancer. These men also tend to eat fewer fruits and vegetables. Doctors aren’t sure which of these factors is responsible for raising the risk. It may explain the low incidence of cancer in Asian men.

Some studies have suggested that men who consume a lot of calcium (through food or supplements) may have a higher risk of developing prostate cancer. Dairy foods (which are often high in calcium) might also increase risk. 

Research, however, does indicate that some foods may decrease your chance of contracting prostate cancer. 

Tomatoes. Tomatoes are high in lycopene, which could have a protective effect against prostate, lung, and stomach cancers. Multiple studies suggest that high levels of lycopene in the blood are linked with a lower risk of prostate cancer and may even help slow the spread of cancerous cells. Cooked tomatoes have a higher concentration of lycopene than raw.

Fruits. Diets high in fruits and vegetables have been shown to protect against many cancers. Lycopene-containing fruits including guava, papaya, and watermelon are recommended. Some research suggests that pectin — a common fiber found in apples, apricots, plums, and citrus fruits and used as a thickener in many jams and marmalades — may reduce the number of cancerous cells by as much as 40 percent. 

Vegetables. A new study from the University of Colorado finds a high-fiber diet rich in vegetables might be why Asian men develop prostate cancer so infrequently compared to Western men. Additionally, researchers have reported that fiber-rich eating could slow the progression of the disease. Other studies have found broccoli and cauliflower to be especially effective in reducing cancer risk because cruciferous veggies slow the growth of cancer cells in the body. 

Medications in Development

Aneustat Shows Promise as a Non-Toxic Drug for Prostate Cancer

Aneustat is an immunotherapy that is truly groundbreaking. It is taken orally and offers substantial efficacy,yet has a negligible side effect profile and presents no known safety risks. It is a multivalent, multifunctional platform drug. It is identified as a platform drug because it has been subject to studies that pair it with a number of currently utilized medications for prostate cancer. Studies indicate that it can significantly increase efficacy, while redicing side effects, and even more importantly, drug resistance. Combination therapy has become an increasingly popular option and Aneustat has been proven to be effective as both a stand-alone medication and as a component of combination therapy while being paired with numerous cancer drugs.

Aneustat is scheduled to begin a phase 3 study in collaboration with Johns Hopkins that will focus on Aneustat with enzalutimide for post-surgical, radiation recurrent prostate cancer, while another study at the Tisch Cancer Center at Mt. Sinai will examine Aneustat in combination with docataxel for metastatic castration resistant prostate cancer. 

Darolutamide

Darolutamide (developmental code names ODM-201, BAY-1841788) is a nonsteroidal antiandrogen (NSAA) – specifically, a selective antagonist of the androgen receptor (AR) – which is under development by Orion and Bayer HealthCare for the treatment of advanced, castration-resistant prostate cancer. 

It is an oral medication and appears to to neglibly cross the blood-brain barrier. This is beneficial due to the reduced risk of seizures and other central side effects. Another advantage is that it does not seem to increase testosterone levels in mice or humans. 

The results of a recent study will soon be published, and early indications are that it compares favorably with enzalutamide (Xtandi) and apalutamide (Erleada), yet may have a more favorable side effect profile. 

VISION Study

A new global phase 3 clinical research study in men with progressive metastatic castration-resistant prostate cancer (mCRPC), called the VISION study, will evaluate the effectiveness and safety of the investigational drug Lu-PSMA-617, in combination with the best standard of care, versus patients treated with best standard of care alone. This research is being conducted by physicians in approximately 80 institutions throughout the US, Canada, and Europe and will include approximately 750 men who are eligible for the trial.

New Combination Therapy 

Pfizer and Astellas have announced that a recent study has indicated that the addition of enzalutamide to standard androgen deprivation (ADT) has led to improved outcomes in men with metastatic, hormone-sensitive prostate cancer (mHSPC). This is the first time that a “second-line” form of androgen deprivation has been shown to have meaningful efficacy in the treatment of any form of hormone-sensitive (as opposed to castration-resistant) prostate cancer.

NEW DRUGS ON THE HORIZON 2019

by Daniel Dupuis

There are a number of new medications in development that offer help for patients suffering from a number of different diseases.

Cancer research, much like last year, is prominent among both small biotech firms, in addition to large pharmaceutical companies. The main focus is on how they might maintain or increase efficacy, while hoping to mitigate life-altering side effects and/or safety concerns.

Many other sectors have also seen some major breakthroughs, among them ALS, Multiple Systems Atrophy, complicated urinary tract infections and chronic migraines.

This list includes some major developments in oncology drug development, in addition to a new treatment for plaque psoriasis and a promising formulation for Alzheimer’s disease. 

Talazoparib For Breast Cancer

Talazoparib is a new medication from Pfizer that is currently in phase 3 trials that offers some hope for women with advanced stage breast cancer (with the BRCA1 and BRCA2 gene mutation). The BRCA gene mutations are common among aggressive breast and ovarian cancers.

Patients that took part in the study lived longer without their cancer progressing by an average of three months more than women treated with standard chemotherapy. While three months may seem to be an incremental change, it is a substantial period of time relevant to improvements within the cancer sector. There are many drugs that have been approved in the past that have improved life expectancy by periods of time that are measured in days, rather than weeks.

In the current trial, researchers found that the women who were randomly selected to receive talazoparib had a higher response rate to treatment than women who received standard chemotherapy: 63 percent versus 27 percent. 

The drug does, however, have side effects. Among women receiving talazoparib, 55 percent had blood disorders, mostly anemia, compared with 38 percent of those receiving standard chemotherapy. 

In addition, 32 percent of the women receiving talazoparib had other side effects, which is only slightly less than the rate of 38 percent for those in the trial that were on standard chemotherapy.

New Drug from Galera Therapeutics Reduces Effects of Radiation

Within the oncology sector, there are a number of approaches to mitigating the life-altering side effects and safety risks associated with cancer therapies, which includes the many immuno-therapies and combination drugs that are currently under investigation. 

Galera Therapeutics has pursued a novel approach to helping reduce a prominent side effect of radiation therapy. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to GC4419 for the reduction of the duration, incidence and severity of mouth lesions induced by radiotherapy for head and neck cancer. 

Results from Galera’s 223-patient, double blind, randomized, placebo-controlled Phase 2b clinical trial demonstrated GC4419’s ability to dramatically reduce the duration of mouth lesions from 19 days to 1.5 days (92 percent), the incidence of lesions through completion of radiation by 34 percent and the severity by 47 percent. It also indicated that GC4419 increased tumor response to radiation therapym while preventing toxicity in normal tissue. Mouth lesions are one of the most commonly cited side effects among people under radiotherapy.

While mouth lesions are its lead indication, GC4419 is also being studied in combination with SBRT for its anti-tumor effect in a Phase 1/2 trial of patients with locally advanced pancreatic cancer.

Aneustat Is a True Breakthrough Medication for Prostate Cancer

Aneustat is an immunotherapy that is truly groundbreaking. It is taken orally and offers substantial efficacy, yet has a negligible side effect profile and presents no known safety risks. It is a multivalent, multifunctional platform drug. It is identified as a platform drug because it has been subject to studies that pair it with a number of currently utilized medications for prostate cancer. Studies indicate that it can significantly increase efficacy, while redicing side effects, and even more importantly, drug resistance. Combination therapy has become an increasingly popular option and Aneustat has been proven to be effective as both a stand-alone medication and as a component of combination therapy while being paired with numerous cancer drugs.

Aneustat is scheduled to begin a phase 3 study in collaboration with Johns Hopkins that will focus on Aneustat with enzalutimide for post-surgical, radiation recurrent prostate cancer, while another study at the Tisch Cancer Center at Mt. Sinai will examine Aneustat in combination with docataxel for metastatic castration resistant prostate cancer. 

New Alzheimer’s Drug Slows Memory Loss in Early Trial Results

The long, discouraging quest for a medication that works to treat Alzheimer’s disease reached a potentially promising milestone. For the first time in a large clinical trial, a drug was able to both reduce the plaques in the brains of patients and slow the progression of dementia.

The drug, currently known as BAN2401, is a result of a cooperative initiative of Eisai, a Japanese company, and Biogen, based in Cambridge, Mass. Eisai is the maker of Aricept, which is one of the few drugs that can help slow early memory decline, but which is effective for only about six to nine months, while Biogen is the maker of another Alzheimer’s treatment, aducanumab, that has shown early promise in a small Phase 1 trial in both reducing amyloid and slowing cognitive decline.

More extensive trials will be needed to know if the new drug is truly effective, but if the results, presented recently at the Alzheimer’s Association International Conference in Chicago, are borne out, the drug may be the first to successfully attack both the brain changes and the symptoms of Alzheimer’s.

Aside from a couple of medications that can slow memory decline for a few months, there is no effective treatment for Alzheimer’s, which affects about 44 million people worldwide, including 5.5 million Americans. It is estimated that those numbers will triple by 2050.

Realistic goals for the current treatment of Alzheimer’s are not focused on cognitive improvement, but instead are merely demonstrating that a drug might slow the progression of the disease. On a battery of cognitive and functional tests measuring memory and skills like planning and reasoning, the performance of the high-dose BAN2401 group declined at a rate that was 30 percent slower than the rate of decline in the placebo group.

Risankizumab Offers New Hope for People with Psoriasis

There is no shortage of drugs used to treat autoimmune conditions. Indeed, two drugs in this class, Humira® and Enbrel®, are currently first and second in overall spending for all medications in the U.S.

Risankizumab is currently being evaluated by the FDA for the treatment of plaque psoriasis, an autoimmune disease. Risankizumab has demonstrated greater efficacy in reducing psoriasis symptoms in clinical trials vs. the currently available medications.

Study participant’s lesions improved by 90%, while also offering complete clearance among some of the subjects. 82% of patients had a 90% clearance rate, while 49% reported 100% clearance.

Looking forward, risankizumab is also being studied for other autoimmune conditions, such as Crohn’s disease and ulcerative colitis.

A NEW STUDY FOCUSES ON A BREAKTHROUGH IMMUNO-ONCOLOGY DRUG COMBINATION

by Daniel Dupuis

A number of immuno-therapies formulations for the treatment of cancer have been developed in a quest to extend patient survival rates, while also mitigating life-altering side effects and safety concerns. While no current or proposed drug can make this claim, a recently published study that was featured in the British Journal of Cancer provides data that indicates that the initial promise of immunotherapies has been realized. 

Previous studies have demonstrated that Aneustat™ is not only effective as a stand-alone oncology therapy, but can also best be described as a “foundational” drug for combination cancer therapy. Aneustat™ has been paired in studies with a wide array of oncology medications that have been recognized as standard-of-care therapies and the results have consistently demonstrated that the addition of Aneustat™ offers dramatically improved outcomes and reduced drug resistance, thereby, expanding the therapeutic window.

A recently published study, Treatment with docetaxel in combination with Aneustat leads to potent inhibition of metastasis in a patient-derived xenograft model of advanced prostate cancer,Qu, et al.,1 11/doi:10,1038/bjc.2017,474, appears in the British Journal of Oncology and assesses the therapeutic advantages of combining Aneustat™ with docetaxel for advanced stage prostate cancer. 

The study utilizes the patient-derived cancer tissue xenograft mode, which is the preferred methodology of the National Cancer Institute. 

Docetaxel + Aneustat™ markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney invasion. This drug combination downregulated expression of cancer driver genes such as FOzM1 (and FOXM1-target genes). 

Aneustat™ has been clinically proven to boost the immune system to kill cancer cells through aptosis, in addition to regulating the metabolic system (tumor microenvironment) to stop proliferation while therapeutically affecting 1750 cancer related genes.

These results confirm earlier results by the same researcher that demonstrated that Aneustat™ alone was more effective than docetaxel for tumor shrinkage and inhibition of cancer cell growth. The combination of docetaxel and Aneustat™, however, was superior to either drug as a single agent.

The significance of this study is considerable in that it not only demonstrates improved efficacy, but offers a combination therapy that is also safer, while reducing the debilitating side effects common to oncology medications. 

This study is a part of a series of studies that demonstrate that Anuestat™ has improved the overall efficacy of a wide array of medications known to be accepted as first-line therapies for prostate cancer, including enzalutamide, bicalutamide, abiraterone and apalutamide. Of even greater significance, however, is that Aneustat™ has been proven to be effective against tumors that have already been deemed to be resistant to these medications. This indicates that the various combination therapies will be viable for a longer period of time than any single agent.

More than 1 in 10 men will be diagnosed with prostate cancer at some point in their lives, and 1 in 41 will die of the disease; making it the second leading cause of cancer death in American men, according to the American Cancer Society. Additionally, a recent report states that while the incidence of most cancers is in decline, late stage prostate cancer has risen since 2015. 

Aneustat™ in combination with docetaxel is a subject of continuing trials and it may be a potential candidate for Fast Track approval by the FDA. This conclusion is based on the FDA giving added weight to formulations that can effectively alter key biomarkers (a key component of the approval of Keytruda for new indications).  Aneustat™ is non-toxic, with a negligible side effect profile (minor nausea) and no apparent safety risks. As a multi-target immuno-therapy it can prevent, rather than be a contributing factor, to the onset of co-morbidities.

This recent study confirms that Aneustat™ is a foundational drug that can be combined with numerous standard of care medications that can improve overall efficacy, while reducing side effects and safety concerns and mitigate the inherent drug resistance associated with current oncology medications.

Aneustat™ was developed by Omnitura that is scheduled for an IPO in 2019.

HOW CAN OBESITY BOTH FUEL TUMOR GROWTH AND HELP NEW IMMUNOTHERAPY DRUGS WORK BETTER?

Rich Haridy

The same obesity-driven process that speeds up cancer growth may also help improve the efficacy of new tumor-killing immunotherapy treatments(Credit: frenta/Depositphotos)

Two new studies have provided compelling insights into the relationship between obesity and cancer. The research reveals fascinatingly paradoxical effects, suggesting obesity can suppress our immune responses to enhance tumor growth, but also improve the efficacy of a new kind of cancer-killing immunotherapy.

The first study, from Trinity College Dublin, focuses on the effect of obesity on a type of immune cell known as natural killer (NK) cells. These cells play a vital role in cancer surveillance, hunting the body for tumor cells, and activating an immune attack when they track then down.

The research revealed that excess fat can fundamentally blunt the anti-tumor responses of NK cells by essentially “clogging up” the cells and inhibiting their cytotoxic machinery. The study suggests that metabolic reprogramming of these NK cells could kick-start their anti-cancer activity, offering a potential new treatment strategy.

The second study, from UC Davis, homed in on another mechanism by which obesity drives tumor growth. It found that leptin, a hormone produced by fat cells in the body, mediated dysfunction in cancer-killing T-cells by increasing the presence of a protein called PD-1.

“In obese animals cancer grows faster because there are more nutrients for tumors and because the immune system is more suppressed,” says William Murphy, co-author of the UC Davis study.

PD-1 essentially acts to turn down immune system activity, and cancer cells can cleverly stimulate that protein to avoid attack from the immune system. A new class of immunotherapy drugs called checkpoint inhibitors work by blocking PD-1 activation, releasing the brake on T-cells to help them better hunt, and kill, cancer cells.

Interestingly, previous research has revealed that these new checkpoint inhibitor drugs are more effective in obese patients. The new study further examined this odd paradoxical outcome confirming in both animal and human cohorts that PD-1 inhibitors are indeed more effective in obese patients compared to non-obese patients.

“It’s counter-intuitive because up to this point all of our studies showed that obesity resulted in more toxicities associated with immunotherapy treatments,” says Murphy. “This is a game-changer because when we personalize medicine and look at body mass index, in some situations it can be bad, and in some situations it can be helpful.”

The hypothesis is that the excess of PD-1 brought on by obesity actually makes the checkpoint inhibitor drugs more effective in activating the body’s T-cells. The UC Davis team do caution that this doesn’t mean cancer patients embarking upon a new checkpoint inhibitor treatment run out and commence a high-fat diet to enhance the drug, but instead the discovery could help better home in on the most effective treatment for individual patients.

“We are not advocating for obesity as improving prognosis for cancer patients,” says Arta Monjazeb, co-last author on the study. “But obesity appears to induce immune suppression and accelerated tumor growth through mechanisms that can be successfully reversed by checkpoint inhibitor immunotherapy.”

It’s clear that while obesity may improve the efficacy of certain new immunotherapies, it also certainly hampers the immune system, and causes tumors to grow more aggressively. Further research from the UC Davis team will explore whether this specific mechanism, that increases the effect of checkpoint inhibitors, can be harnessed to make the new immunotherapy treatment successful in more patients.

The first study was published in the journal Nature Immunology, while the second study appears in the journal Nature Medicine.

Sources: Trinity News, UC Davis

https://newatlas.com/obesity-cancer-immune-system-checkpoint-inhibitor/57195/

NATURALLY OCCURRING PRODUCTS IN CANCER THERAPY

Rajesh, Leena S. Sankari, L. Malathi, and Jayasri R. Krupaa

Author information Article notes Copyright and License information Disclaimer

This article has been cited by other articles in PMC.

Abstract

Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment.

KEY WORDS: Carcinogenesis, curcumin, quercetin

Oral cancer is defined as the cancer of mouth and pharynx including cancer of lips, tongue, floor of the mouth, palate, gingiva, alveolar mucosa, buccal mucosa, oropharynx, tonsils, uvula and salivary glands. Cancer is the biggest cause of mortality worldwide, responsible for 8.2 million death/year and rising according to the global scientific report released on the February 5, 2014.[1] Factors such as obesity, poor diet, tobacco, radiation, environmental pollutants, lack of physical activity and age increases cancer risk. These factors may cause cancer by damaging genes directly and/or indirectly in combination with existing genetic mutation within cells.[2]

Epidemiology

Epidemiological studies have shown that diet containing fruits and vegetables reduce the risk of several types of cancer.[3] Intake of fruits and vegetables has been successfully used in the prevention of chronic disease associated with oxidative stress condition including cancer.[4,5] WHO projects 10,000,000 cases of cancer per year worldwide and 6,000,000 deaths from cancer per year worldwide. And it also projected 15 million cases/year in 2020. It is been estimated that 80% of the world population relies on plant-based medicine for primary health care and 75% of all pharmaceuticals were discovered by examining the use of plants in traditional medicine.

Carcinogenesis

The transformation of normal cell to cancer cell occurs through three distinct phases, initiation, promotion, and progression. Initiation of cancer occurs in the normal cells due to exposure of carcinogenic and mutagenic agents. The initiated cells are irreversibly altered and are at greater risk of neoplastic transformation. However, initiation alone is not sufficient for tumor formation.[6] In promotion phase, tumor promoters convert the initiated cells into neoplastic cells.[7,8] Progression involves a stepwise evolution of neoplastic cells into higher degree of malignancy.

Chemopreventive Agents in Oral Carcinogenesis

Various phytochemicals obtained from vegetables, fruits, spices, teas, herbs, and medicinal plants, such as flavonoids carotenoids, phenolic compounds and terpenoids, have been extensively investigated for their anti-cancer activities due to their safety, low toxicity and general availability.[9] In this article we discuss (a) use of phytochemicals, including curcumin, resveratrol, apigenin, quercetin, genistein, lycopene, isothiocyanates (b) their mechanism of action, such as anti-oxidant properties, inhibition of cell cycle, induction of apoptosis, regulation of angiogenesis.

Curcumin

Curcumin (diferuloylmethane), a yellow pigment belongs to the class of polyphenols present in the rhizomes of turmeric is used in cooking in India. It is also used as a cosmetic and in some medical preparations. Multiple therapeutic activities of curcumin have also been considered to be associated with its anti-oxidant and anti-inflammatory properties. The anti-inflammatory effect of curcumin is most likely medicated through its ability to inhibit cyclooxygenase-2, lipoxygenase (LOX), and inducible nitric oxide synthase.[10] Curcumin has the capability to inhibit carcinogen bioactivation via suppression of specific cytochrome P450 isozymes, as well as to induce the activity or expression of phase II carcinogen detoxifyingenzymes.[11] Combination of phenethylisothiocyanate and curcumin caused suppression of epidermal growth factor (EGF) receptor phosphorylation and inhibition of EGF-induced phosphorylation and induction of phosphatidylinositol 3-kinase in prostate cancer-3 cells.[12] It regulates tumor cell growth through multiple cell signaling pathways, including cell proliferation pathway, cell survival pathway, caspase activation pathway, tumor suppressor pathway, death receptor pathway, mitochondrial pathways and protein kinase pathway.

Resveratrol

Resveratrol (trans-3, 5, 4-tryhydroxystilbene) a naturally occurring phytoalexin, is found at a high concentration in the skin of red grapes and red wine. Resveratrol is known to have anti-oxidant, anti-inflammatory and antiproliferative effects on a variety of cancer cells in vitro and in various animal models.[13] Resveratrol has been identified as an effective candidate for cancer prevention based on inhibitory effects on cellular events associated with cancer initiation, promotion, and progression.[14] It has been shown to inhibit tumor necrosis factor-α-mediated matrix metalloproteinase-9 expression in HepG2 cells by down regulation of the nuclear factor-kB signaling pathway.[15] Various studies revealed multiple intracellular targets of resveratrol, which affect cell growth, inflammation, apoptosis, angiogenesis, and invasion and metastasis.[16]

Apigenin

Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables possesses anti-oxidant, anti-mutagenic, anti-carcinogenic, anti-inflammatory, anti-growth, and anti-progression properties.[17] Apigenin is effective in carcinogenesis, topical application of apigenin inhibited dimethyl benzanthracene-induced skin tumors,[18] and also diminished ultraviolet-induced cancer incidence and increased tumor free survival experiment.[19]

Earlier studies demonstrated that the apigenin promotes metal chelation, scavenges free radicals and stimulates phase II detoxification enzymes in cell culture and in vivo tumor models.[20]

Quercetin

Quercetin is a dietary flavonoid abundant in variety of foods including apples, berries, brassica vegetables, grapes, onions, shallots, tea, and tomatoes as well as many seeds, nuts, barks and leaves.[21] It usually occurs as o-glycosides with D-glucose as glycosides have been identified.[22] Among polyphenols, quercetin is one of the most potent anti-oxidants, as demonstrated in different studies.[23,24] It has been shown to inhibit oxidative species generating enzymes such as xanthine oxidase, LOX, and nicotinamide adenine dinucleotide phosphate oxidase.[25] It is a potent anti-cancer agent, exhibiting different activities such as cell cycle regulation, interaction with type II estrogen binding sites and tyrosine kinase inhibition.[26]

Isothicyanates

Isothiocyanates (ITCs) are electrophilic compounds that play a major role in potential chemopreventive effects associated with high intake of cruciferous vegetables such as watercress, brussel sprouts, broccoli, cabbage, horseradish, radish, and turnip.[27] Cruciferous vegetables have been widely accepted as potential diet components that may decrease the risk of cancer.[28] Epidemiological studies show that the dietary intake of ITCs I associated with reduced risk of certain human cancers.[29] ITCS display anti-carcinogenic activity by reducing the activation of carcinogens and increase their detoxification.

Genistein and ursolic acid

Genistein is an isoflavone compound found in soybean and related products such as tofu, soy milk and soy sauce.[30] And is a promising cancer chemotherapeutic agent.[31] It inhibits the growth of cancer by increasing apoptosis, including cell cycle delays and modulating intercellular signaling pathways.[32]

Ursolic acid is a pentacyclic triterpene compound widely found in food, medicinal herbs, apple peel and is able to exhibit a wide range of pharmacological functions, including anti-oxidant, anti-tumor, anti-inflammatory activities.[33]

Conclusion

Natural products play a major role in chemotherapy drugs, and primarily target proliferating tumor cells. Chemoprevention by phytochemicals is of great interest and is considered to be an inexpensive, readily applicable, acceptable, and accessible approach to cancer control and management. Several phytochemicals are in preclinical or clinical trials for cancer chemoprevention. Epidemiological studies have shown that high dietary consumption of vegetables and fruits reduced the risk of cancer. Severe toxicity is a major drawback in conventional radiotherapy and chemotherapy.

Footnotes

Source of Support: Nil

Conflict of Interest: None declared.

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THIS NEW, FDA-APPROVED SKIN CARE DRUG COULD HELP OVER 7.5 MILLION PEOPLE

Julie Ricevuto , Digital Beauty Editor | November 12, 2018

Photo Credits: pumatokoh/Shutterstock/Model Is Used for Illustrative Purposes Only

Alleviating psoriasis symptoms has been a difficult feat to achieve for decades, but with new advances in the skin care industry, doctors are excited that a cure may be closer than ever before. While we still haven’t reached a final remedy yet, a new advancement in the treatment of psoriasis has people super excited. Bryhali Lotion 0.01% is a new topical treatment that uses an active ingredient called halobetasol to treat the condition. And as Allure reports, Bryhali Lotion has just been approved by the Food and Drug Administration, making doctors and patients alike excited to give the new medication a try.

The treatment, which is a “super-potent corticosteroid,” is used on affected skin and is attained through a prescription. It works to calm the inflamed skin caused by plaque psoriasis—the most common form of psoriasis—which often presents itself as dry, raised, red skin lesions covered with silvery scales.

You May Also Like: An Injection to Erase Cellulite Might Be Coming Very Soon

Unlike other psoriasis medications, Bryhali Lotion is proven to be safe for a longer time period (8 weeks!) than its competitors. Most psoriasis drugs are only considered safe for a two week period because they’ve been proved to thin the skin with additional use, however, this didn’t happen to users in clinical trials that tested Bryhali Lotion for the full eight weeks.

“Bryhali Lotion will help address an unmet need for many plaque psoriasis patients,” said Lawrence J. Green, M.D., a lead investigator on the Bryhali Lotion Phase 3 studies and associate clinical professor of Dermatology at George Washington University School of Medicine, in a press release. “Topical steroids are the most frequently used treatment for psoriasis, but come with an increased risk of adverse events and a duration of use limited to two to four weeks. With Bryhali Lotion, I’m excited to offer my patients a topical steroid option that can be used for up to eight weeks without sacrificing tolerability, and with proven efficacy.”

Possible side effects of the treatment include burning, stinging, itching and dryness at the application site, so be sure to talk to your doctor if you experience any of these symptoms when using the product. Regardless of these side effects, we can’t help but be excited about Bryhali Lotion’s FDA approval. Considering psoriasis affects 7.5 million people, it’s possible this could make a big difference in a lot of lives.

https://www.newbeauty.com/blog/dailybeauty/12564-bryhali-lotion-psoriasis-treatment-fda-approval/

ARGENTUM PHARMACEUTICALS WINS PATENT INVALIDATION TRIAL AGAINST THE SOLE REMAINING PATENT PROTECTING JANSSEN’S ZYTIGA

By Mike Botta

https://www.rdmag.com/news/2018/01/j-j-loses-zytiga-patent-protection-ruling-argentum-challenge

Argentum Pharmaceuticals wins patent invalidation trial against the sole remaining patent protecting Janssen’s Zytiga.

The U.S. Patent & Trademark Office (PTO) issued a final written decision Wednesday in Argentum Pharmaceuticals LLC’s inter partes review (IPR) against the sole unexpired patent covering Janssen Oncology, Inc.’s Zytiga (abiraterone acetate). Janssen Oncology is a subsidiary of Johnson & Johnson.

Johnson & Johnson said it is evaluating its options concerning a possible rehearing request or appeal, according to a company statement.

Argentum had challenged all claims (1−20) of Janssen’s U.S. Patent No. 8,822,438, which the FDA’s Orange Book states will expire in August 24, 2027.

In the decision, the PTO concluded that Argentum “satisfied its burden of demonstrating, by a preponderance of the evidence, that the subject matter of claims 1–20 would have been obvious,” and therefore ordered “that claims 1-20 are held unpatentable.

“The inter partes review process is an important tool by which generic and biosimilar companies can create prescription drug savings by ensuring that non-innovative patents do not block competition,” Argentum’s CEO Jeffrey Gardner said following the decision. “Argentum’s core mission is to lower the cost of prescription drugs by challenging patents that are not innovative and which artificially support high drug prices.”

Johnson & Johnson, meanwhile, issued the following statement: “We are disappointed in and strongly disagree with the U.S. Patent and Trademark Office’s (USPTO) decisions relating to Zytiga as part of the inter partes reviews. We are evaluating our options with respect to a request for rehearing and/or appeal to the Court of Appeals for the Federal Circuit. We believe the ‘438 patent is valid and will continue to vigorously defend it.”

But, Argentum’s Gardner expressed confidence that, if appealed, the decision would be upheld: “We believe that the PTO’s decision will be upheld if appealed by Janssen, and will save the U.S. healthcare system billions of dollars over the next decade. Those savings will inure to the benefit of American patients by improving their access to the high quality, safe, and effective FDA-approved generic alternatives that they deserve.”

Zytiga is used along with prednisone to treat men with prostate cancer that is resistant to medical or surgical treatments and that has spread to other parts of the body.

NEW IMMUNOTHERAPY TECHNIQUE CAN SPECIFICALLY TARGET TUMOR CELLS, UCI STUDY REPORTS

“Lab on a chip” technology can be used to create individualized treatments for cancer

November 6, 2018

“This technology is particularly exciting because it dismantles major challenges in cancer treatments,” Weian Zhao says. Steve Zylius / UCI

Irvine, Calif., Nov. 6, 2018 — A new immunotherapy screening prototype developed by University of California, Irvine researchers can quickly create individualized cancer treatments that will allow physicians to effectively target tumors without the side effects of standard cancer drugs.

UCI’s Weian Zhao and Nobel laureate David Baltimore with Caltech led the research team that developed a tracking and screening system that identifies T cell receptors with 100-percent specificity for individual tumors within just a few days. Research findings appear in Lab on a Chip. (Link to study: https://pubs.rsc.org/en/content/articlepdf/2018/lc/c8lc00818c?page=search)

In the human immune system, T cells have molecules on their surfaces that bind to antigens on the surface of foreign or cancer cells. To treat a tumor with T cell therapy, researchers must identify exactly which receptor molecules work against a specific tumor’s antigens. UCI researchers have sped up that identification process.

“This technology is particularly exciting because it dismantles major challenges in cancer treatments,” said Zhao, an associate professor of pharmaceutical sciences who is affiliated with the Chao Family Comprehensive Center and the Sue & Bill Gross Stem Cell Research Center. “This use of droplet microfluidics screening significantly reduces the cost of making new cancer immunotherapies that are associated with less systemic side effects than standard chemotherapy drugs, and vastly speeds up the timeframe for treatment.”

Zhao added that traditional cancer treatments have offered a one-size-fits-all disease response, such as chemotherapy drugs which can involve systemic and serious side effects.

T cell receptor (TCR)-engineered T cell therapy, a newer technology, harnesses the patient’s own immune system to attack tumors. On the surface of cancer cells are antigens, protruding molecules that are recognized by the body’s immune system T cells. This new therapy places engineered molecules on the patient’s T cells which will bind to their cancer cell antigens, allowing the T cell to destroy the cancer cell. TCR therapy can be individualized, so each patient can have T cells designed specifically for their tumor cells.

This antigen-TCR recognition system is very specific – there can be hundreds of millions of different types of TCR molecules. A big challenge for TCR-T cell therapy development remains in identifying particular TCR molecules out of a pool of millions of possibilities. Finding a match can take up to a year (time many cancer patients don’t have) and can cost half a million dollars or more per treatment.

By using miniscule oil-water droplets, Zhao’s team designed a device that allows for individual T cells to join with cancer cells in microscopic fluid containers. The TCRs that bind with the cancer cells’ antigens can be sorted and identified within days, considerably faster than the months or year that previous technologies required. The technology also significantly reduces the cost of making individualized TCRs and accelerates the pipeline of TCR-T cell therapy to clinic.

Through a partnership with Amberstone Biosciences, a UCI start-up, this entire platform and screening process will be available to pharmaceutical companies for drug development within just a few months. Not only can this technology help revolutionize TCR-T cell therapies for cancer, but it will also be a powerful tool for discovering other immunological agents, including antibodies and CAR-T cells, and for elucidating new immunology and cancer biology at a depth not possible before.

Aude I. Segaliny, Lingshun Kong, Ci Ren, and Xiaoming Chen of UCI contributed to this work, in addition to Guideng Li, Jessica K. Wang and Guikai Wu. This work was supported by UCI Applied Innovation, the Chao Family Comprehensive Cancer Center, the Sue & Bill Gross Stem Cell Research Center and the Department of Pharmaceutical Sciences. The work was funded by National Institutes of Health (grants 1DP2CA195763 and R21CA219225) and Amberstone Biosciences LLC: No. AB-208317.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit www.uci.edu.

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