Breast cancer therapies face resistance from pathway alterations

A new review in the journal Oncotarget examines how breast cancer cells resist therapy. The article, published on March 13, 2025, is authored by Dinara Ryspayeva and a team from Brown University. Breast cancer is the most common cancer among women and a leading cause of cancer-related deaths. While many patients initially respond to treatment, some cancers can return or stop responding altogether. The review highlights how changes in cell communication and growth can help tumors survive and resist treatment. The authors focus on several important signaling pathways that affect breast cancer, such as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK, and others. These pathways control essential processes like cell growth and DNA repair. Mutations or alterations in these pathways can lead to tumor progression and treatment resistance. One key pathway discussed is PI3K/Akt/mTOR. It is often overactive in many breast cancers, especially in hormone receptor-positive and HER2-positive types. The review notes that 25-40% of breast cancer cases show changes that activate this pathway, highlighting its importance in cancer growth. Another pathway, RAS/RAF/MEK/ERK, can promote tumor growth as well. It may become active even without mutations, particularly in HER2-positive and triple-negative breast cancers. The review also mentions new treatments being developed to target these pathways. Some are already approved, while others are still in the testing phase. Combining treatments may help block multiple pathways at once, making it harder for cancer cells to adapt. Overall, this review offers valuable insights for researchers and doctors. Understanding how breast cancer cells resist treatment could lead to more personalized and effective strategies for patients with aggressive cancers.