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Most breast cancers depend on estrogen to grow. This dependence explains why hormone-based treatments, such as aromatase inhibitors, are among the most effective therapies for estrogen receptor–positive breast cancer. Despite their success, these treatments do not work indefinitely for all patients. Over time, many tumors adapt to estrogen deprivation and continue to survive, grow, and spread. This process, known as aromatase inhibitor resistance, represents a major clinical challenge and is often associated with more aggressive disease and poorer outcomes. One reason resistant breast tumors are difficult to treat is that cancer cells adapt their internal signaling systems. Instead of relying on estrogen, they activate alternative growth pathways, including the MAPK and PI3K/AKT pathways. These pathways promote cell survival, movement, and resistance to therapy and are frequently driven by proteins such as KRAS and related G-proteins, which have historically been difficult to target. A recent study published in Oncotarget suggests now that a new class of compounds may offer a way to overcome this resistance. Full blog - https://www.oncotarget.org/2026/01/13/overcoming-aromatase-inhibitor-resistance-in-breast-cancer-a-new-therapeutic-strategy/ Paper DOI - https://doi.org/10.18632/oncotarget.28759 Correspondence to - Nazarius S. Lamango - nazarius.lamango@famu.edu Abstract video - https://www.youtube.com/watch?v=8xQEilloO9Q Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28759 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PCAIs, ROS, MAPK, PI3K/AKT, LTLT-Ca cells To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM