Jeanne Tie, MBBS, FRACP, of Ludwig Colon Cancer Initiative Biomarker Laboratory, Australia, is the recipient of the 2009 Bradley Stuart Beller Merit Award for her research, “Selecting subjects for a therapeutic target in colorectal cancer (CRC): Using a clinical database to enrich for patients harboring the BRAFV600E mutation” (Abstract 11003). Dr. Tie will present her award-winning research on Monday, June 1, during the Tumor Biology and Human Genetics Oral Abstract Session (9:30 AM-12:30 PM, West Hall F5).
Dr. Tie’s reaction to learning she had received this award was “utter disbelief,” she said. “I feel extremely honored to be bestowed with this award. I am very grateful for the vision and guidance from my supervisors and mentors at the Ludwig Colon Cancer Initiative: Dr. Jayesh Desai, Dr. Peter Gibbs, Dr. Lara Lipton, and Dr. Oliver Sieber.”
The role of BRAFV600E mutation in cancer has received considerable attention since its discovery in 2002 and is believed to be as carcinogenic as KRAS; it also has been found to be a predictor of resistance to anti-EGFR antibodies. According to Dr. Tie, one of the reasons why therapeutics designed to target the RAS/RAF MAPK signaling pathway have failed to show significant clinical benefit is the lack of patient selection for the specific molecular target in clinical trials. A promising BRAFV600E inhibitor for melanoma is in a phase I trial, and this study is being expanded to include patients with colorectal cancer harboring the BRAF mutation.
“Due to the low mutation rate of BRAFV600E in colorectal cancer, it would be useful if we could enrich the population to be screened by selecting patients with certain clinical features associated with the BRAF mutation,” Dr. Tie told ASCO Daily News. “The frequency of BRAF mutation in rectal cancer is not known, and there is limited data on the prognostic significance of the BRAF mutation in colorectal cancer and the concordance of BRAF mutation between primary tumors and their matched metastases. These are important clinical information when designing a phase II or III clinical trial involving the BRAFV600E inhibitor.”
Merit Awards are presented to 100 oncology fellows each year who are the first authors of outstanding Meeting abstracts. This award, funded through the Bradley Stuart Beller Endowment, is awarded to the fellow who has the highest ranked abstract at the Annual Meeting as determined by the Scientific Program Committee. It was created by Ronald E. Beller, PhD, and his wife, Judith, in collaboration with The ASCO Cancer Foundation® Board of Directors. Dr. Beller — former ASCO Vice President and Chief Operating Officer — developed the award upon his retirement from ASCO and The ASCO Cancer Foundation, in memory of his son, Bradley Stuart Beller. It was presented for the first time in 2007.
This study is Dr. Tie’s first experience with bench research, and she noted that mastering different molecular techniques was a challenge; however, such a challenge also comes with great rewards. She enjoys being part of an “enthusiastic team of scientists and oncologists engaging in practice-changing translational research, linking molecular changes in tumors to clinical data and patient outcomes, with the hope of finding new prognostic and predictive biomarkers in colorectal cancer,” she said. “It is a very exciting field where the standard of care is constantly evolving with new knowledge and discoveries.”
This investigation has several implications for future research and patient care. Dr. Tie’s research demonstrated that the colorectal cancer population harboring the BRAF mutation can be enriched by selecting older, female patients with right-sided colon cancers. The study showed that primary tumors that are wild-type for BRAF do not develop the mutation in their metastases, implying that analysis of BRAF status in the primary tumors is sufficient to select patents for treatment with BRAF inhibitor.
The study shows good concordance of BRAF mutation status between primary tumors and their matched metastases, implying that repeat biopsies of metastatic sites are not necessary, Dr. Tie noted.
“Data also suggest that patients with metastatic colon cancer harboring the BRAFV600E mutation tend to be older and have a poorer prognosis compared with their wild-type counterparts. The poorer outcome associated with the BRAFV600E mutation may be explained by the aggressive nature of the BRAF-mutant colon cancer, their innate resistance to standard chemotherapies or both,” Dr. Tie said. All of these results “will need to be taken into consideration during the clinical development of the BRAFV600E inhibitor, tailoring to the patient subset most likely to benefit from this small molecule.”
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