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colon cancer

Peter Westcott, on right, in the lab with technicians Zakeria Aminzada, on left and Colin McLaughlin, center. Photo by Steven Lewis

By Daniel Dunaief

When Peter Westcott was growing up in Lewiston/Auburn, Maine, his father Johnathan Harris put the book “Human Genome” on his bed. That is where Westcott, who has a self-described “obsessive attention to detail,” first developed his interest in biology.

Westcott recently brought that attention to detail to Cold Spring Harbor Laboratory, where he is an assistant professor and Cancer Center member. He, his wife Kathleen Tai and their young children Myles and Raeya moved from Somerville, Massachusetts, where Westcott had been a postdoctoral fellow at the Koch Institute of Integrative Cancer Research at the Massachusetts Institute of Technology.

Westcott will take the passion and scientific hunger he developed and honed to the famed lab, where he plans to continue studies on colon cancer and the immune system.

“A lot of things attracted me to Cold Spring Harbor Laboratory,” said Westcott who had been to the lab during conferences, joining three Mechanisms and Models of Cancer meetings, and appreciated that the small size of the lab encourages collaboration and the sharing of ideas across disparate fields.

At this point, Westcott, who purchased a home in Dix Hills and started on campus on September 1st, has two technicians, Zakeria Aminzada and Colin McLaughlin working with him. He will be taking on a graduate rotation student from Stony Brook University soon and would also like to add a postdoctoral researcher within about six months. He plans to post ads for that position soon. 

Research directions

Westcott said his research has two major research directions.

The first, which is more translatable, involves looking at how T cells, which he described as the “major soldiers” of the immune system, become dysfunctional in cancer. These T cells balance between attacking unwanted and unwelcome cells relentlessly, disabling and destroying them, and ignoring cells that the body considers part of its own healthy system. When the T cells are too active, people develop autoimmunity. When they aren’t active enough, people can get cancer.

“Most cancers, particularly the aggressive and metastatic ones, have disabled the immune response in one way or another, and it is our focus to understand how so we can intervene and reawaken or reinvigorate it,” he explained.

During cancer development, T cells may recognize that something on a tumor is not healthy or normal, but they sometimes don’t attack. Depending on the type of genetic program within the T cells that makes them tolerant and dysfunctional, Westcott thinks he can reverse that.

A big push in the field right now is to understand what the genetic programs are that underlie different flavors of dysfunction and what cell surface receptors researchers can use as markers to define T cells that would allow them to identify them in patients to guide treatment.

Westcott is taking approaches to ablate or remove genes called nrf4a 1, 2 and 3. He is attacking these genes individually and collectively to determine what role they play in reducing the effectiveness of the body’s immune response to cancer.

“If we knock [some of these genes] out in T cells, we get a better response and tumors grow more poorly,” he said.

Westcott is exploring whether he can remove these genes in an existing T cell response to cause a regression of tumor development. He may also couple this effort with other immunotherapies, such as vaccines and agonistic anti-CD40 antibody treatment.

As a second research direction, Westcott is also looking more broadly at how tumors evolve through critical transitions. Taking an evolutionary biology perspective, he hopes to understand how the tumors start out as more benign adenoma, then become malignant adenocarcinoma and then develop into metastatic cancer. He is focusing in particular on the patterns of mutations and potential neoantigens they give rise to across the genome, while concentrating on the immune response against these neoantigens.

Each tumor cell is competing with tumor cells with other mutations, as well as with normal cells. “When they acquire new mutations that convey a selective advantage” those cells dominate and drive the growth of a tumor that can spread to the rest of the body, Westcott said.

Using a mouse model, he can study tumors with various mutations and track their T cell response.

T cells tend to be more effective in combating tumors with a high degree of mutations. These more mutated tumors are also more responsive to immunotherapy. Westcott plans to study events that select for specific clones and that might shift the prevalence, or architecture, of a tumor.

Some of the work Westcott has done has shown that it is not enough to have numerous mutations. It is also important to know what fraction of the cancer cells contain these mutations. For neoantigens that occur in only a small fraction of the total cells in the tumor, the T cell responses aren’t as effective and checkpoint blockade therapy doesn’t work.

He wants to understand how the T cell responses against these neoantigens change when they go from being subclonal “to being present in most or all of the tumor cells,” he explained. That can occur when a single or few tumor cells acquire a selective advantage. His hypothesis is that these selective events in tumor progression is inherently immunogenic. \

By exploring the fundamental architecture of a tumor, Westcott hopes to learn the mechanisms the tumor uses to evade the immune system.

Ocean breeze

As Westcott settles in at CSHL, he is excited by the overlap between what he sees around the lab and the Maine environment in which he was raised.

“Looking out the window to the harbor feels like New England and Maine,” he said. “It’s really nostalgic for me. Being near the ocean breeze is where I feel my heart is.”

Before his father shared the “Human Genome” book with him, Westcott was interested in rocks and frogs. In high school, his AP biology teacher helped drive his interest in the subject by encouraging discussions and participation without requiring her students to repeat memorized facts. The discussions “brought to life” the subject, he said.

As for his work, Westcott chose to study colon cancer because of its prevalence in the population. He also believes colon cancer could be a model disease to study all cancers. By understanding what differentiates the 12 percent of cases that are responses to immunotherapy from the remainder that don’t respond as well to such approaches, he hopes to apply these lessons to all cancer.

“There is a huge, unmet need,” he said.

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Dr. Kanika Kaur

Colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States, yet it is one of the most preventable types of cancer. For 2021, the National Cancer Institute reported nearly 150,000 new cases diagnosed with approximately 53,000 fatalities. Affecting men and women of all racial and ethnic groups, colorectal cancer is most often found in people age 50 and older.

One of the biggest challenges physicians face when discussing colorectal cancer is debunking myths surrounding identifying and treating the disease. Catholic Health Gastroenterologist Kanika Kaur, MD, addressed what she commonly hears from patients.

Myth: There is nothing I can do to lessen my risk of colon cancer.

Fact: There is a lot people can do to reduce their risk of colon cancer. A diet low in red meat and processed meat, high in fruits and vegetables is very important. Smoking is a well-known risk factor for colon cancer along with many other cancers. Also, regular exercise may reduce your risk of developing colorectal cancer. The single biggest modifiable risk factor for colorectal cancer is failure to be screened. Colorectal cancers develop from pre-cancerous polyps, which are growths on the lining of the colon and rectum. Screenings detect and allow doctors to remove polyps before they become cancerous.  Colonoscopy with polyp removal reduces the risk of developed colon cancer by up to 90%

Myth: Colorectal cancer is fatal.

Fact: Colorectal cancer is highly treatable, especially when detected early. More than 90% of patients with a localized cancer that is confined to the colon or rectum are alive five years after diagnosis. Sadly, about only one-third of colorectal cancers are diagnosed at an early stage. A majority of cases are identified when the disease has spread beyond the wall of the colon or rectum and to other parts of the body. This decreases the chances of the cancer being cured.

Myth: I should only have a screening if I have symptoms.

Fact: This is false. The reality is that early colorectal cancer usually has no symptoms. This is why it is important to get screened. It is recommended all men and women age 45 and older should have a screening. Those with a personal or family history of colon cancer, a history of inflammatory bowel disease and those with symptoms such as rectal bleeding are considered at high risk and may need to be screened before the age of 45. Additionally, women with a personal or family history of ovarian, endometrial or breast cancer may also need to be screened at an earlier age.

Myth: Only those with a family history of colon cancer are at risk.

Fact: Nearly three-quarters of all new colorectal cancer cancers are with individuals with no known risk factors for the disease.

Myth: Colorectal cancer affects only older, white men.

Fact: Colorectal cancer impacts men and women. Additionally, people of color are more likely to be diagnosed with colorectal cancer in its advanced stages, suggesting that they may require colon cancer screening at a younger age.

Myth: A colonoscopy is a difficult procedure.

Fact: A colonoscopy is not painful. The most unpleasant part of the procedure is the preparation that is required the day before the exam. But this is important as an inadequate prep may lead to missed findings such as polyps or a need to repeat the procedure.

Myth: Finding a colon or rectal polyp means I have cancer and need surgery.

Fact: A polyp is a pre-cancerous lesion that, if not treated, can progress to cancer. If polyps are detected early and removed before they can progress, colon cancer can be prevented. Colonoscopy and sigmoidoscopy have been shown to prevent deaths from colon cancer – a fact that has been well demonstrated over time. Most polyps are treated by removing them during the colonoscopy. Even large polyps can be removed without surgery. 

More information on Catholic Health’s comprehensive colorectal cancer and digestive health services may be found by visiting chsli.org. To find a Catholic Health physician near you, please call (866) MY-LI-DOC.

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