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This Pancreatic Cancer Breakthrough Is Big News

By Sean Williams – Feb 28, 2016 at 3:08PM

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New findings from the University of Glasgow offer a key that will help doctors and the pharmaceutical industry more effectively target the weaknesses of what has been, up till now, one of the most treatment-resistant and lethal cancers.

Image source: Pixabay.

According to the American Cancer Society's "2015 Cancer Facts & Figures" report, nearly 1.66 million Americans were expected to be diagnosed with cancer in 2015, while more than 589,000 cancer sufferers were expected to die of the disease. Cancer has become the second-leading cause of death in the U.S., trailing only heart disease, and its rising incidence rate is expected to push it to the top spot.

While the very word "cancer" sends shivers down people's spines, some cancer diagnoses are far worse than others. For example, diagnoses of prostate cancer, thyroid cancer, and breast cancer yielded five-year survival rates of better than 99%, 98%, and 91%, respectively, based on ACS data between 2004 and 2010. The stage at which a patient's diagnosis is made is also a key factor in their survival outlook.

By comparison, people with some other cancer types fared quite poorly. Though their outlooks have improved over the past three-plus decades, people diagnosed with brain cancer, esophageal cancer, and lung cancer still have five-year survival rates of just 35%, 20%, and 18%, respectively.

And sitting consistently at the bottom of the survival range is pancreatic cancer, with a five-year survival rate between 2004 and 2010 of just 7%. Nearly as many people will die from pancreatic cancer in a given year as from breast cancer, though nearly five times as many people are diagnosed with breast cancer annually.

Image source: National Institutes of Health.

This pancreatic cancer breakthrough is big news
For years, pancreatic cancer has baffled researchers. Most medicines thrown at the disease have provided marginal improvements at best. However, new research from the University of Glasgow published in the journal Nature offers new hope to pancreatic cancer patients.

The researchers say they've discovered that there are four different subtypes of pancreatic cancer: squamous, pancreatic progenitor, immunogenic, and aberrantly differentiated endocrine exocrine, or ADEX. These subtypes describe the differentiating factors between them, and being able to recognize them provides a chance to make therapies more targeted to the weaknesses of each patient's subtype. In short, the ability to recognize these characteristics of a cancer makes the disease more treatable.

While similarities were observed between the squamous subtype of pancreatic cancer and the types of squamous tumors observed in breast and lung cancer, and the pancreatic progenitor and ADEX classes provided some degree of differentiation based on early and late-stage pancreatic cancer development, it's the immunogenic subtype that excites researchers the most. Specific mechanisms observed by researchers in this subtype suggest that they may be responsive to the cancer immunotherapies currently on the market or being studied. Immunotherapies work to turn off the mechanism in cancer cells that prevents the immune system from recognizing them as invaders to be targeted, while simultaneously kicking a patients' immune system into high gear.

Leanne Reynolds, head of research for Pancreatic Cancer UK, which supports the University of Glasgow's research, explained: "If we can predict more accurately which treatment would be most effective for each patient, we can ensure patients have the best chance of living for as long as possible, as well as possible."

Immunotherapies at the ready
A number of already-approved cancer immunotherapies, as well as clinical-stage immunotherapies, stand at the ready to join the fight against pancreatic cancer.

Image source: Merck & Co.

Merck's (MRK -0.60%) Keytruda and Bristol-Myers Squibb's (BMY -0.86%) Opdivo, both checkpoint inhibitors targeting PD-1, have been approved to treat certain metastatic melanoma patients, and second-line metastatic non-small cell lung cancer patients (although Opdivo's NSCLC indication is for all patients, whereas Keytruda only targets high PD-L1 expressing-patients). What researchers have discovered with these new treatment options offered by Merck and Bristol-Myers Squibb is that they typically work best in combination with existing cancer therapies, or in combination with other immunotherapies. This is why we're seeing dozens of trials run by both companies, with most being for those drugs in combination with existing therapies.

One exception to that was the KEYNOTE-010 study of Keytruda, which was an open-label phase 2/3 study testing two doses of Keytruda versus docetaxel in previously treated squamous and non-squamous NSCLC patients that expressed PD-L1. High-expressing patients (i.e., those with more than 50% of tumors expressing PD-L1) receiving Keytruda saw their overall survival rate improve by 46% in the 2 mg/kg dose group and 50% in the 10 mg/kg dose group, compared to docetaxel. Assuming those results for Keytruda (and Opdivo) carry over into the squamous and immunogenic pancreatic cancer subtypes, we could see a marked improvement in response rates and overall survival.

Image source: Bristol-Myers Squibb.

NewLink Genetics (NLNK) is another cancer immunotherapy developer taking aim at pancreatic cancer. Its leading treatment candidate is algenpantucel-L, which induces the expression of a carbohydrate known as alpha-gal, which we've built up a natural immunity to, in cancer cells. The alpha-gal, when processed by the immune system, serves as a teacher, so to speak, that allows the immune system to recognize other pancreatic cancer cells expressing alpha-gal as well.

In an open-label phase 2 study involving 69 patients with resected pancreatic cancer, algenpantucel-L delivered impressive results. After testing a 100 million cell dose and a 300 million cell dose, they found the 300 million cell dose proved most effective. After one year, 96% of patients were still alive, no patients experienced a grade 4 adverse event, and 81% remained disease-free. Considering the disappointingly high recurrence rate of even resected pancreatic cancer, this was a promising result. NewLink has a fully enrolled phase 3 trial known as IMPRESS for algenpantucel-L ongoing.

The point is simple: Now that the medical community has a better understanding of what they are fighting in pancreatic cancer, researchers can angle their attacks to target the newly revealed potential weak points. Change is unlikely to happen overnight, but don't be surprised if response rates and overall survival rates for pancreatic cancer finally make a leap forward in the coming five to 10 years.

Sean Williams has no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen name TMFUltraLong, track every pick he makes under the screen name TrackUltraLong, and check him out on Twitter, where he goes by the handle @TMFUltraLong.

The Motley Fool has no position in any of the stocks mentioned. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy

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