Molecular Subtyping of Rectal Cancers Can Guide Prognosis, Treatment and Future Screening

MedicalResearch.com Interview with:

Y. Nancy You, MD, MHSc Associate Professor Section of Colorectal Surgery Department of Surgical Oncology Medical Director Familial High-risk Gastrointestinal Cancer Clinic University of Texas MD Anderson Cancer Center

Dr. Y. Nancy You

Y. Nancy You, MD, MHSc
Associate Professor
Section of Colorectal Surgery
Department of Surgical Oncology
Medical Director
Familial High-risk Gastrointestinal Cancer Clinic
University of Texas MD Anderson Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite the progress in the treatment of many cancers, colorectal cancer (CRC) remains the third most common and lethal cancer in the US. Over 130,000 people are expected to be diagnosed and over 50,000 patients will die from CRC this year. In the recent years, the most exciting development has been our understanding of the molecular complexity of CRC.

Currently, four major molecular subtypes of colorectal cancer are recognized. Our study focuses on the Consensus Molecular Subtype 1, which accounts for up to 15% of CRCs, and is characterized by a deficiency in DNA mismatch repair (dMMR), a high level of mutations (i.e. hypermutated), by instability in parts of the genome called microsatellites, and by strong immune activation. Prior to our study, patients with rectal cancer that belong to this molecular subtype have represented an unknown, in terms of their prognosis, and how the tumors respond to current treatments. More importantly, this molecular subtype harbor a genetic condition that can be transmitted within the family called “Lynch Syndrome”. So we designed our study to fill these gaps in our understanding that exist in this subtype of CRCs and to highlight key clinical care issues related to the caring for patients with a genetic syndrome.

The main findings are that rectal cancers belonging to this molecular subtype have favorable prognosis, respond well to standard chemoradiation, and are linked to Lynch Syndrome and should be treated at centers with expertise in hereditary cancer syndromes.

MedicalResearch.com: What should readers take away from your report?

Response: First, patients should realize that so much progress has been made in the molecular diagnosis of cancer today that we are able to test for DNA mismatch repair deficiency in the tumor and use it to guide clinical care.

Second, rectal cancers with this type behave very favorably.

Third, it is important to get tested for Lynch Syndrome. If suspected, then they should consider being referred to a center with expertise in hereditary cancer syndromes, because they will not only need to be treated for their rectal cancer but also need lifelong surveillance for cancers that can develop in other organs. Also the blood relatives of the patients should be counseled to consider genetic testing as well.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study represents a small prototype example of what precision medicine can promise. By knowing the molecular change in the tumorr, we can understand the implications toward prognosis, drug/treatment response, and can impact on the long-term care of the patient and potentially family members.

MedicalResearch.com: Is there anything else you would like to add?

Response: Because we are testing more and more tumors for more and more gene mutations, more studies like this one will need to be conducted, so both the patient and the providers can really understand what is the clinical meaning of a gene mutation and what practical implementation does it have for clinical care.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:
N. de Rosa, M. A. Rodriguez-Bigas, G. J. Chang, J. Veerapong, E. Borras, S. Krishnan, B. Bednarski, C. A. Messick, J. M. Skibber, B. W. Feig, P. M. Lynch, E. Vilar, Y. N. You. DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics. Journal of Clinical Oncology, 2016; DOI: 10.1200/JCO.2016.66.6826

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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