WASHINGTON, DC – Innovative new gene-based approaches for combating colon cancer have been identified by scientists from the laboratory of Michael Brattain, PhD, Senior Vice President for Basic Research and Chairman of the Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute (RPCI). Their research will be presented at the 97^th Annual Meeting of the American Association for Cancer Research, April 1-5, in the Washington Convention Center, Washington, DC.*

The PIK3CA gene encodes the PI3K catalytic subunit p110 alpha. Mutations in this gene are common in human colon cancer. In the first study (Abstract 3047), researchers found that mutant PIK3CA colon cancer cells can survive and continue to grow in starvation for several days, while most wild type cells died. Mutant PIK3CA cells were found to have constitutive high PI3K activity, thus, contributing to the relative high malignancy. Tumors in nude mice with mutant PIK3CA grew and spread more rapidly, indicating that PIK3CA mutations promote primary tumor growth and metastasis. These findings indicate that mutant PIK3CA imparts a more aggressive phenotype in colon cancer and could be a potential therapeutic target for treatment of colon cancer patients with PIK3CA mutations.

            IGF1R and EGFR have been implicated in colon cancer tumorigenesis. Inhibition of either receptor leads to apoptosis of human malignant cells. However, co-expression of these receptors is found in a subset of colon cancers, and inhibition of one receptor in a single drug application stimulates the activity of the other.

This suggested that a combination of antagonists to both receptors would be very effective in this subtype of colon carcinomas. In the second study (Abstract 5073), Compound II, a novel antagonist of IGF1R, and Tarceva, EGFR targeted therapy, were used to target these receptors simultaneously in order to test this concept. Results indicate that the combination of drugs was synergistic and thus significantly more effective than the single drugs in inhibiting the growth of human colon cancer cells. Targeting both receptors was associated with the induction of apoptosis.  

Founded in 1907, the American Association for Cancer Research is the world’s oldest and largest professional organization dedicated to advancing cancer research. Members include more than 24,000 basic, translational and clinical researchers, health care professionals, and cancer survivors and advocates in the United States and in more than 60 other countries.

Roswell Park Cancer Institute, founded in 1898, is the nation’s first cancer research, treatment, and education center and is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers. For more information, visit RPCI’s website at www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org

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*Editor’s Note:

Abstract # 3047 - “Characterization of Colon Cancer Cells Bearing Only Wild-Type or Mutant PIK3CA Allele” Embargoed until Monday, April 3, 1 pm

Exhibit Hall, Washington Convention Center, Poster Session: Molecular Mechanisms of Tumorigenesis; Identities of Novel Targets

Abstract # 5073 “The Combination Treatment with Inhibitors Targeting the Type 1 Insulin-like Growth Factor Receptor (IGF1R) and the Epidermal Growth Factor Receptor (EGFR) in Human Colon Cancer”

Embargoed until Wednesday, April 5, 8 am  

Exhibit Hall, Washington Convention Center, Poster Session: Inhibitors of Signal Transduction in Cancer.