Overcoming Aromatase Inhibitor Resistance in Breast Cancer: A New Therapeutic Strategy
Jan 13, 2026
Explore the challenge of aromatase inhibitor resistance in breast cancer, where tumors adapt and activate new growth pathways like MAPK and PI3K/AKT. Discover the innovative PCAI compounds that target resistant cells by inducing stress and raising reactive oxygen species, triggering cell death. The discussion highlights how these compounds disrupt cell structure and movement, potentially limiting metastasis. Exciting future research steps include safety testing and clinical evaluation, offering hope for more effective treatments.
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insights INSIGHT
Estrogen-Independent Tumor Adaptation
Aromatase inhibitor resistance occurs when tumors adapt to estrogen deprivation and activate alternative growth pathways.
This resistance makes tumors more aggressive and reduces the effectiveness of hormone therapies.
insights INSIGHT
Alternative Growth Pathways Drive Resistance
Resistant cells activate MAPK and PI3K/AKT pathways to drive survival and movement.
Targeting these internal signaling adaptations could be key to overcoming resistance.
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PCAIs Show Potent Effects In Lab Models
Researchers tested polyisoprenylated cysteinylamide inhibitors (PCAIs) on letrozole-resistant LTLT-Ca cells.
One PCAI, NSL-YHJ2-27, markedly reduced survival and induced lasting changes in cell proliferation.
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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
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Keywords - cancer, PCAIs, ROS, MAPK, PI3K/AKT, LTLT-Ca cells
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