Dr Salani on Research With MEK Inhibition in KRAS-Mutant Serous Ovarian Cancer

Ritu Salani, MD, MBA, gynecologic oncologist, director, Gynecologic Oncology, University of California, Los Angeles (UCLA), UCLA Health, discusses pathways in low-grade serous ovarian cancer that may be viable for targeted therapy development, as well as potential reasons why prior research with MEK inhibitors have shown suboptimal results.

One of the pathways involved low-grade serous ovarian cancer is the hormone pathway, Salani begins. Many patients with low-grade serous ovarian cancers tend to have high estrogen-receptor and progesterone-receptor expression levels, making them more susceptible to hormonal targeting, she explains. Studies are ongoing to investigate the replacement of chemotherapy with hormone strategies as well as the use of adjuvant hormonal therapies, she reports. These approaches could be compelling alternatives, Salani emphasizes

Another emerging target for drug development is the KRAS pathway, Salani continues. Mutations in this pathway are frequently found in patients with low-grade serous ovarian cancers, and targeting this pathway has proven effective in patients who do not harbor a KRAS mutation, she reports. MEK inhibitors can be used to inhibit KRAS signaling in KRAS-mutant tumors. Although MEK inhibitors have demonstrated favorable outcomes, progress is slow, and they have yet to significantly alter the standard of care or the overall treatment landscape for low-grade serous ovarian cancer, Salani says.

Several challenges may have impeded the progress of research in this field, she states. One major issue is the rarity of low-grade serous ovarian cancer, which makes it difficult to recruit enough participants to clinical trials in a timely fashion, Salani says. Despite recruitment challenges, some promising signals have been observed. Another significant issue is the adverse effects (AEs) associated with MEK inhibitors, she notes. Many patients with low-grade serous ovarian cancer are young women, and the AEs can be particularly debilitating for them. For instance, MEK inhibitors can cause severe rashes, often on the face, which can be very disruptive and require treatment breaks. This AE can accordingly limit the continuous administration of therapy, complicating treatment protocols, Salani explains. Despite these obstacles, research aiming to leverage hormonal and KRAS pathways remains promising, she concludes.