Among the first cancer drug combinations were mixtures of several chemotherapies that resulted in better and longer-lasting responses than individual drugs could deliver. Then came targeted therapies and immunotherapies, which were combined with chemotherapies and with each other to increase the proportion of patients who respond and the duration of those responses. While many cancer drug combinations were discovered by empirically testing opportunistic and random pairings, others were based on biological hypotheses that one drug could complement the other. Below are a few of the strategies behind recently successful and still investigational combos.
Coadministering two targeted agents that work on different targets within the same signaling pathway is a way to stave off cancer resistance. Combining two targeted agents that block molecules within different pathways is one common strategy.
EXAMPLE: In 2014, the FDA approved the first combination: dabrafenib, a B-raf inhibitor, plus trametinib, a MEK inhibitor, for advanced melanoma. The two drugs target different molecules within the Ras signaling pathway (left). The combination of lenvatinib, an anti-VEGF oral drug, and everolimus, an oral mTOR inhibitor, was approved by the FDA for renal cell carcinoma in 2016. The drugs target two separate but cancer-linked signaling pathways that support tumor growth (right).© THOM GRAVES
