Scientists at The University of Texas MD Anderson Cancer Center in Houston have identified a new class of gene mutations that may contribute to outcomes in the treatment of ovarian cancer.
Research on the gene family known as ADAMTS could open up a new genetic avenue for the design of ovarian cancer therapies, say the researchers publishing their work in the journal JAMA Oncology.
The research affects those ovarian cancers that do not have mutations in BRCA1 or BRCA2 – the tumor-suppressing genes known for higher risks of ovarian and breast cancers when mutated.
These mutations are found in only around a fifth of ovarian cancer patients, who generally respond better to chemotherapy. The remaining patients, however, respond to platinum-based chemotherapy and are the focus of this study.
The authors outline the importance of the investigations: “Drug resistance is a major cause of treatment failure in ovarian cancer and primarily contributes to the disease’s high mortality rate.”
The paper continues:
“The early identification of patients who are (or are not) benefiting from platinum-based therapy is central to advancing ovarian cancer management and represents an important step toward the goal of personalized treatment.”
The study examined data from the Cancer Genome Atlas to determine association between novel gene mutations in ovarian cancer and overall survival of patients, survival without cancer progression and response to chemotherapy.
The team looked the years 2009 to 2014 and identified mutations from eight members of the ADAMTS family among the 512 cases of cancer studied.
The results showed a significantly higher rate of sensitivity to chemotherapy within the group with these mutations. Wei Zhang, PhD, professor of pathology at MD Anderson, says of the study’s findings:
“This suggests that events other than BRCA1 or BRCA2 mutations exist that predict chemotherapy response.”
Prof. Zhang is excited by the study’s findings because, he says, ovarian cancer remains the leading cause of death from women’s cancer in spite of aggressive surgery and chemotherapy.
Most patients eventually experience relapse, mainly as a result of chemotherapy resistance. Prof. Zhang says:
“The study’s findings are exciting because early identification and differentiation of patients with chemotherapy-resistant disease could allow enrollment in clinical trials with alternative therapeutics rather than ineffective chemotherapy.”
“This new information on ADAMTS mutations may be a useful addition to BRCA mutation assessment for patients with ovarian cancer,” he adds.
First author of the study Luexin Liu, PhD, assistant professor of pathology at MD Anderson, adds:
“We concluded that ADAMTS mutations may contribute to outcomes in ovarian cancer cases without BRCA1 or BRCA2 mutations and this may have important clinical implications.”
“We found no statistical correlation between ADAMTS and BRCA1 or BRCA2 mutations,” she notes.