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Penn Research Holds Promise for Patients with Advanced Colon Cancer

Colon cancer is the most common of gastrointestinal (GI) cancers and the third leading cause of cancer-related deaths in in the United States, but it’s also largely preventable and often curable with early detection.

Thanks to an increase in education and awareness around the disease, greater numbers of Americans are getting screened. Since colonoscopies also serve to prevent cancer by allowing pre-cancerous polyps to be removed, rates of diagnosis are declining.

In the last 10 years, colon cancer incidence rates for people over age 50 have dropped by over 30 percent, according to the American Cancer Society.

“We’re moving the needle,” said Greg Ginsberg, MD, professor of Medicine in the Gastroenterology Division and director of Endoscopy Services at Penn Medicine. “We recommend that patients with no known risk factors or symptoms begin colonoscopy screening at age 50 with the test repeated every 10 years following normal results. Screening is still the most effective way to save lives.”

But, for those who are diagnosed at advanced stages, treatment options quickly become limited and the five-year survival rate plummets.

This is precisely the group of patients that Penn Medicine GI researchers are working diligently to help.

“When patients come to us with symptoms — which can include anemia or rectal bleeding — they are often already at stage II or greater, with the cancer rampant within the colon and on the verge of spreading to other organs, often requiring chemotherapy and other interventions to improve their outcomes,” said Arturo Loaiza-Bonilla, MD, assistant professor of Clinical Medicine and an oncologist in the division of Hematology/Oncology who treats patients with colon and other GI cancers.

Patients with a genetic predisposition and a strong family history of colon cancer, which includes up to 30 percent of all cases, represent one avenue for understanding the disease in order to move toward new treatment options for patients in advanced stages of the disease. Patients with common inherited genetic mutations which can increase a person’s risk for developing colon cancer are cared for by the physicians in the Penn GI Cancer Genetics program under the leadership of Anil Rustgi, MD, chief of Gastroenterology, and a nationally-known expert in the genetics of gastrointestinal cancers and experimental therapeutics and Bryson Katona, MD, PhD, an instructor of Gastroenterology. These patients have conditions including Lynch syndrome, which is caused by a genetic mutation associated with early onset colorectal cancer; familial adenomatous polyposis and MYH associated polyposis, both of which can lead to leading to an abnormal proliferation of benign polyps in the large intestine which can also become cancerous; and Peutz-Jeghers syndrome, found in children and characterized by the development of noncancerous growths called hamartomatous polyps, benign tumor-like malformations in the GI tract, and more.

Rustgi’s lab is looking deep within the genome to better understand and define the genetic pathways that can lead to a colon cancer. “By understanding the roads that lead to tumor development and growth, we believe we can develop new therapies to intercept these signals and prevent tumors from developing,” Rustgi explained.

In addition, Rustgi and colleagues are also investigating the possibility of spurring the body’s own immune system to fight colon cancer in patients with what is known as microsatellite instability (MSI), which accounts for 15 percent of colorectal malignancies. In patients with MSI, tumor cells mutate rapidly within the cell’s DNA that would normally prevent damage. Researchers are considering immunotherapy with a new class of cancer drugs known as ‘immune checkpoint inhibitors’ – which have shown promising results among patients with advanced melanoma, another notoriously deadly cancer --to tell immune cells to attack the mutating tumor cells. By removing the blindfold of our defense cells with these engineered molecules, it can be possible for the immune system to get rid of the cancer, similarly to when a bacteria or virus enters our bodies.

Researchers are also looking to examine the potential relationship between the gut bacteria (microbiome) and colon cancer in future research studies.

Finally, through Penn’s Center for Personalized Diagnostics (CPD), clinicians are testing all stage IV patients, in whom the cancer has spread beyond the colon, to try to identify their specific disease mutations.

Using this next generation DNA sequencing technology, they are able to determine the genetic makeup of the cancer and help refine diagnoses with greater precision than standard imaging tests and blood work by spotting known mutations that can inform the treatment plan.

Rustgi and Loaiza-Bonilla are excited at the progress being made and are looking to new research to change the game for patients with advanced colon cancer in stages III and IV.

“In the next three to five years,” Rustgi said, “we are hopeful that we will have new, potentially life-saving treatments for these patients for whom we currently have little to offer.”

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