Combination therapy can prevent resistance to treatment in hormone responsive metastatic breast cancer patients

Medical Xpress / Instituto de Medicina Molecular / Cell Reports Medicine ^ | July 13, 2023 | Sandra Casimiro et al

[ConservativeMind]

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 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 study 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, 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.

"We studied the possibility that the RANK signaling pathway could be relevant in the resistance to treatment in the case of luminal breast cancer," explains Sandra Casimiro.

"In this study, we found that high levels of RANK in cancer cells are associated to resistance to treatment with CDK4/6 inhibitors. By analyzing a dataset of human samples of tumors from patients treated with CDK4/6 inhibitors, we found that the levels of RANK in the tumor increase overtime during the duration of the treatment. This suggests that RANK can be implicated in acquired resistance as well," continues Sandra Casimiro.

"Having this in mind, we tested in vitro and in mouse models if inhibiting the RANK pathway in combination with the current therapy would improve treatment efficacy, and found that the cancer cells respond better to the treatment in the presence of RANK ligand inhibitors."

"The pharmacological inhibition of RANK pathway is already used in the clinical setting," concludes Luís Costa,

[ConservativeMind]

It appears at least two drugs are out there that work as RANK ligand inhibitors. One is “Medroxyprogesterone acetate,” and the other is “Denosumab” (also known as Prolia and Xgeva).

Medroxyprogesterone appears to be well under $10 a prescription, on GoodRX.

[ConservativeMind]

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