Combination Therapy May Prevent Resistance for Some Breast Cancers
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Breast cancer is a heterogeneous disease, but 70% of cases are characterized by the presence of hormone receptors for estrogen, progesterone, or both. The first line of treatment for these patients, when presenting with metastatic disease, is endocrine therapy in combination with CDK4/6 inhibitors, but the majority develops resistance to treatment within two years. Now, a new study led by Sandra Casimiro, staff scientist at the Instituto de Medicina Molecular João Lobo Antunes (iMM; Portugal), and Luís Costa, principal investigator at the iMM and oncologist at the Hospital Santa Maria (Portugal), and published today in the scientific journal Cell Reports Medicine*, found a promising molecular target in cancer cells that could be used in combination with the standard care to avoid resistance to treatment in metastatic breast cancer.
“Currently, the first-line of care treatment for metastatic luminal breast cancer, which expresses receptors for estrogen and/or progesterone, is the combination of endocrine therapy with CDK4/6 inhibitors. Although this treatment was a life-changing discovery for breast cancer patients, around 20% are irresponsive and the majority of the ones who respond to treatment becomes resistant within 2 years”, says Luís Costa, oncologist and co-leader of the study.
“The pharmacological inhibition of RANK pathway is already used in the clinical setting. Our study suggests that combination therapy with RANK ligand inhibitors and the current standard care for metastatic luminal breast cancer could improve the outcome in non-responsive patients and avoid or delay the resistance to treatment”, concludes Luís Costa, on the clinical relevance of these findings. Upon clinical studies, RANK ligand inhibition could represent a promising add-on to the current standard care treatment for hormone responsive breast cancer.
Reference: Gomes I, Gallego-Paez LM, Jiménez M, et al. Co-targeting RANK pathway treats and prevents acquired resistance to CDK4/6 inhibitors in luminal breast cancer. Cell Rep Med. 2023. doi: 10.1016/j.xcrm.2023.101120
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