Skip Navigation

Novel cause of ovarian cancer drug resistance identified

  • Panos Konstantinopoulos, MD, PhD

    Dana-Farber Cancer Institute scientists have shed new light on why some ovarian cancers don’t respond to or learn to evade standard chemotherapy and targeted drugs. They say the discovery could aid in developing strategies to combat ovarian drug resistance.

    The investigators’ research, posted online by the journal Cell Reports, identified a previously unknown resistance culprit – a tiny piece of genetic material called a microRNA, or miRNA – that the cancer cells use to regain their DNA repair powers.

    The study focused on the 15 to 20 percent of epithelial ovarian cancers harboring inherited BRCA1 and BRCA2 mutations. Because such tumors can’t repair damage to their DNA effectively, are vulnerable to platinum-based chemotherapy agents and newer targeted drugs called PARP inhibitors that shred the tumors’ DNA molecules.

    While these drugs are often effective, a substantial number of patients don’t respond to them or become resistant to the drugs, reducing their long-term survival. One way that BRCA1 and 2 -mutant ovarian tumors outwit treatment is by gaining additional mutations that restore their molecular DNA-repair pathways.

    In the new research, however, senior authors Dipanjan Chowdhury, PhD and Panos Konstantinopoulos, MD, PhD of Dana-Farber Cancer Institute discovered a different resistance mechanism that that doesn’t involve acquiring new mutations. Instead, the ovarian cancer cells turn off one of two competing DNA repair pathways and turn on another pathway, known as homologous recombination (HR) that enables the tumor to resist platinum drugs and PARP inhibitors. This repair pathway switch occurs in cancer cells that make increased levels of a specific micro-RNA, miR-622, which turns out to be a regulator of DNA repair.

  • PanagiotisPanos A Konstantinopoulos
  • Research
  • Ovarian Cancer
  • Media Contacts

    For all inquiries, call 617-632-4090 and ask to speak to a member of the media team. Please direct emails to media@dfci.harvard.edu.

  • Appointments and Second Opinions

    For adults: 877-442-3324
    For children: 888-733-4662

    Make Appointment Online