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Genomic Differences Found in Two Types of Cervical Cancer

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Key Points

  • A high-throughput molecular analysis of 80 cervical tumor samples (40 adenocarcinomas and 40 squamous cell carcinomas) has found high rates of mutations in two genes: PIK3CA and KRAS.
  • While PIK3CA mutations appeared in both cervical cancer subtypes, KRAS mutations were found only in adenocarcinomas.
  • The research suggests that clinical outcomes may be improved with the use of more targeted treatment strategies, including P13 kinase inhibitors and MEK inhibitors.

A study by Alexi Wright, MD, MPH, and colleagues at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston has found that two common subtypes of cervical cancer, adenocarcinoma and squamous cell carcinoma, have distinct molecular profiles. The results suggest that clinical outcomes may be improved with the use of more targeted treatment strategies, including P13 kinase inhibitors and MEK inhibitors. The study is published in Cancer.

The researchers performed high-throughput molecular analysis on 80 cervical tumor samples (40 adenocarcinomas and 40 squamous cell carcinomas) to determine the rates and spectrum of somatic mutations present and identify the rates of “targetable” oncogene and tumor-suppressor gene mutations in cervical cancer.

The analysis revealed validated mutations in 60.0% (48/80) of the tumors examined. The highest mutation rates were found in two genes: PIK3CA (31.3%) and KRAS (8.8%); EGFR had a mutation rate of 3.8%. While PIK3CA mutations were found in both adenocarcinoma and squamous cell carcinomas (25.0% vs 37.5%, respectively, = .33), KRAS mutations were found only in adenocarcinomas. A novel EGFR mutation was detected only in squamous cell carcinomas (0% vs 7.5%, = .24).

Study Results Present New Strategies for Treatment

“This study is important because cervical cancer has been grossly understudied,” said Dr. Wright, Medical Oncologist at Susan F. Smith for Women’s Cancers at Dana-Farber Cancer Institute and lead author of the study. “The results from this study suggest two new strategies for treating cervical cancer. The first strategy is using PIK3 kinase inhibitors, which should work in both adenocarcinoma and squamous cell carcinomas. And the second strategy is using drugs that target KRAS mutations, most likely in combination with chemotherapy.”

According to the American Cancer Society, about 12,340 new cases of invasive cervical cancer will be diagnosed in 2013, and about 4,030 women will die from the disease. Worldwide, cervical cancer is the second leading cause of deaths among women and is responsible for 275,000 deaths annually.

Funding for this study was supported in part by (MRSG-13-013) from the American Cancer Society and a Conquer Cancer Foundation of ASCO Career Development Award to Dr. Wright and philanthropic funds from the Team Maureen Cervical Cancer Fund and the Friends of the Dana-Farber Cancer Institute.

The following study authors reported paid consultancies: Dr. William Hahn (Novartis, Blueprint Medicines, Thermo Fisher), Dr. Andrea Myers (Sanofi Aventis, EISAI). Dr. Nikhil Wagle reports a paid consultancy and stock ownership (Foundation Medicine). Dr. Myers is a paid employee of Novartis.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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