Game-Changing News: Researchers May Have Discovered the Cause of Intestinal Cancer

By Markets Fool.com


Source: Flickr user Erik Soderstrom.

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Cancer is currently the second-leading cause of death in the United States, and if the World Health Organization is correct, it may wind up eclipsing heart disease for the dubious top spot sometime in the near future.

According to the WHO, cancer incidence is expected to rise from 14 million diagnoses to 22 million, globally, over the next two decades. On one hand this news may not be as terrifying as it first sounds, as people are living longer than ever around the world, and age is one of the greatest universal risk factors for developing cancer. Then again, an increase of 8 million cancer cases isn't good news no matter how you twist the story.

Researchers turn their attention to intestinal cancer
One cancer type in particular that researchers are placing near the top of their list to tackle is colorectal cancer. Per the American Cancer Society, colon (also known as your big intestine) and rectal cancer combined accounted for close to 137,000 cancer diagnoses in 2014. Add in the small intestine and you have nearly 9,200 more cases (although cancer of the small intestine in far less common). Yet what makes intestinal cancer so terrifying, and especially colorectal cancer, is that it's the second-leading cause of cancer-related death, behind only lung and bronchus cancer. The ACS estimates colorectal cancer led to more than 50,000 deaths in 2014.

I don't want to shed a completely negative light on how far we've come in terms of treating colorectal and intestinal cancers, because we have observed steady improvements. Between 1975 and 1977, colon cancer five-year survival rates were just 51%. Between 2003 and 2009 that figure had jumped to 65%! The real key here is the ability to detect cancer early. Colon and rectum cancer detected in a local state results in the average patient surviving five years 90% of the time. If they discover the cancer has metastasized, however, that five-year survival rate drops to a disappointing 13%.

The statistics have spoken, and they strongly suggest drug developers work hard toward creating the next generation of intestinal cancer treatments. The good news is researchers have heard this cry loud and clear.

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A game-changing study on intestinal cancer
This past week researchers from Sanford-Burnham Medical Research Institute delivered what could be some game-changing news for those living with intestinal cancer.

Source: AstraZeneca.

According to the 12-author study published online in Cell Reports last week, signaling molecules found in intestinal stem cells could be the culprit behind tumor formation and proliferation. Researchers have long suspected that stem cells, which are responsible for differentiating into other cells throughout our lifetime, can house genetic mutations that when built up can lead to tumor formation.

Specifically, researchers focused on the single layer of epithelial cells that surround the intestines. The growth and replacement of these cells happens every three-to-five days, and is regulated by intestinal stem cells. Researchers discovered that protein kinase C-zeta, or PKC-zeta for short, plays a key role in maintaining balance for this cellular replacement. Too much PKC-zeta and cell regeneration slows down; too little and it speeds up, potentially leading to tumor formation.

Using a mouse model, the authors identified beta-catenin and YAP as tumor promoting agents, and suggested that beta-catenin and YAP as regulators of PKC-zeta function could be the next potential targets for drug developers looking to suppress intestinal tumor development.

Furthermore, the study implied that focusing on beta-catenin and YAP to bring PKC-zeta levels back to normal could help promote epithelial regeneration and healing after chemotherapy and/or radiation therapy.

Of course, one thing you'll want to keep in mind here is that translating from a mouse model over to human clinical studies doesn't always work. Additionally, PKC-zeta may be just one mechanism by which intestinal cancers form, so it's unlikely to be the only solution to ending intestinal cancer occurrence.


Source: AstraZeneca.

New and developing treatments
At the moment there are few, if any, beta-catenin and YAP-targeted drugs in clinical studies, although you'll find no shortage of abstracts detailing their possible connection to tumor growth.

Looking back, the only prior clinical study I was able to dig up targeting PKC-zeta levels involved Roche'sRituxan (which primarily treats blood-borne cancers) being examined as a PCK-zeta-targeting therapy for follicular lymphoma patients in 2008. But just because we aren't seeing many of these targeted clinical drugs yet doesn't mean that they aren't working their way through laboratory and preclinical testing.

On a more visible basis we do have a handful of possible pharmaceuticals options, and one new diagnostic option, which may help intestinal cancer patients wage war against this terrible disease.

On the diagnostic front we witnessed Exact Sciences' non-invasive colon cancer test, known as Cologuard, get approved this past summer. Cologuard works by looking for abnormalities in a patients' DNA. The DNA is extracted from a patients' stool sample, which is sent to Exact Sciences laboratory for analysis. Exact Sciences then looks for clues based on cells shed from the inside of the intestinal wall. Any abnormalities would result in Exact Sciences suggesting a patient be further examined via a colonoscopy. In the clinical study that led to its approval, Cologuard correctly identified 92% of colorectal cancers and 42% of advanced adenomas.

On the drug development side, cancer immunotherapies are where many researchers are focusing. Cancer vaccines are designed to enhance your body's immune system so it can better recognize and attack cancer cells. While there are a number of immuno-oncology players, two in particular stand out.

Source: Bristol-Myers Squibb.

First, Bristol-Myers Squibb's Opdivo is being examined in a number of early stage studies as a possible treatment for colorectal cancer. Opdivo has already cleared the hurdle of being approved by the Food and Drug Administration as a late line of defense against metastatic melanoma. What really drew the attention of physicians, and investors, is that Opdivo generated a response in nearly a third of patients, and was often durable for months at a time. While that might not seem like a lot on paper, remember that most advanced melanoma patients in its trial had tried two or likely more therapies prior and progressed.

The other name to monitor here is AstraZeneca , which is studying its anti-PD-1 cancer vaccine MEDI-4736 in a midstage clinical trial. In phase 1 studies of various solid tumors, including colorectal cancer, AstraZeneca announced that clinical activity was maintained for a year, with 19% of patients achieving a partial response and 39% of patients achieving disease control. MEDI-4736, along with Opdivo, could offer significant quality of life improvements for colorectal cancer patients sooner rather than later.

One step at a time
Researchers appear to be inching closer to discovering the underlying cause of many different types of cancers, including intestinal cancers. While I fully understand that much more research is needed, I'm also strongly encouraged by the results we've witnessed coming from cancer research institutes and universities.

Ultimately there are opportunities here for everyone. Investors could see their nest egg grow as they invest side-by-side with cancer vaccine developers eager find new labels for their key drugs, and more importantly, friends and family members with intestinal cancer can have a chance at improved quality of life and overall survival. Finding a cure is not out of the question, and I hope to see it happen at some point in my lifetime.

The article Game-Changing News: Researchers May Have Discovered the Cause of Intestinal Cancer originally appeared on Fool.com.

Sean Williamshas no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen nameTMFUltraLong, track every pick he makes under the screen nameTrackUltraLong, 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 servicesfree for 30 days. We Fools don't all hold the same opinions, but we all believe thatconsidering a diverse range of insightsmakes us better investors. The Motley Fool has adisclosure policy.