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Breast cancer (BCa) is a devastating disease, which has a high prevalence and mortality in women. BCa metastasis is a major cause of mortality, and bone metastasis accounts for the majority of BCa-associated deaths. The luminal B subtype of BCa is immunogenically low and has the highest propensity to form bone metastasis compared to other BCa subtypes. Recent efforts have targeted BCa with immune checkpoint inhibitor (CPI) therapy. Although some clinical success in other BCa subtypes, luminal BCas had limited success. This has led to combining immune-stimulating therapies with CPIs to enhance the effectiveness of CPI therapy. We have demonstrated that a natural methyl donor, S-adenosylmethionine (SAM), has significant anti-cancer effects in various cancer models including all subtypes of BCa. Here, we show that SAM in combination with anti-PD-1 antibody has an enhanced anti-cancer efficacy compared to SAM, anti-PD-1 antibody, and control. The combination significantly reduced primary tumor growth and metastasis to lungs and bone. Hence, combining SAM with CPI has the potential to treat luminal B BCa.

Breast cancer (BCa) is the most prevalent cancer in females and has a high rate of mortality, especially due to increased metastasis to skeletal and non-skeletal sites. Despite the marked clinical accomplishment of immune checkpoint inhibitor (CPI) therapy in patients with several cancers, it has had limited success in luminal subtypes of BCa. Accordingly, recent efforts have focused on combination therapy with CPI, including epigenetic modulators, to increase …