4/3/2018 Infographic: Cancer Drug Pairings | The Scientist Magazine®

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Infographic: Cancer Drug PairingsResearchers use several different strategies to deliver a onetwo punch.

By Anna Azvolinsky | April 1, 2018

mong the first cancer drug combinations were mixtures of several chemotherapies that resulted inbetter and longerlasting responses than individual drugs could deliver. Then came targeted

therapies and immunotherapies, which were combined with chemotherapies and with each other toincrease the proportion of patients who respond and the duration of those responses. While many cancerdrug combinations were discovered by empirically testing opportunistic and random pairings, others werebased on biological hypotheses that one drug could complement the other. Below are a few of thestrategies behind recently successful and still investigational combos. 

Doubling Up on Targeted TherapyCoadministering two targeted agents that work on different targets within the same signaling pathway isa way to stave off cancer resistance. Combining two targeted agents that block molecules within differentpathways is one common strategy.

Immunotherapy-Chemotherapy, Radiation, or Targeted Therapy.As chemotherapy, radiation, or targeted therapies kill cancer cells, neoantigens are released, helping theimmune system recognize tumor cells. These therapies also minimize tumor burden, buying time for theimmune system to act. Simultaneously, checkpoint inhibitors ramp up the immune response.

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EXAMPLE: In 2014, the FDA approved the first combination: dabrafenib, a Braf inhibitor, plus trametinib, a MEKinhibitor, for advanced melanoma. The two drugs target different molecules within the Ras signaling pathway (left).The combination of lenvatinib, an antiVEGF oral drug, and everolimus, an oral mTOR inhibitor, was approved by theFDA for renal cell carcinoma in 2016. The drugs target two separate but cancerlinked signaling pathways thatsupport tumor growth (right).© THOM GRAVES

EXAMPLE: In 2017, the FDA approved the combination of the chemotherapies pemetrexed and carboplatin, plus thecheckpoint inhibitor pembrolizumab, for advanced lung cancer.© THOM GRAVES

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DUAL CHECKPOINT INHIBITOR ANTIBODY COMBINATION: Combining two checkpoint inhibitors that targettwo different checkpoint pathways is one strategy to stimulate a greater and possibly more durable antitumorimmune response.

EXAMPLE: The only currently a pproved immunotherapy combination is ipilimumab plus nivolumab for metastaticmelanoma. Other checkpoint inhibitor combinations arecurrently in clinical trials.

© THOM GRAVES

CHECKPOINT INHIBITOR PLUS A CELLBASED THERAPY: Also seen as a way to target two different pathwaysto amplify the immune response and potentially overcome resistance.

EXAMPLE: Still theoretical, with no combinations yet approved or in clinical trials

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You

© THOM GRAVES

CHECKPOINT INHIBITOR PLUS A VIRAL VACCINE: A vaccine, in theory, should increase the presentation ofcancer neoantigens to the immune system, bolstering the immune system’s response to a checkpoint inhibitor.

EXAMPLE: The cancer vaccine talimogene laherparepvec, a genetically engineered herpes virus, plus ipilimumab iscurrently in a Phase 2 trial for advanced melanoma, with some positive preliminary data.

© THOM GRAVES

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Tagspharmacology, pharmaceuticals, pharma, immunotherapy, drug development, cancer drugs and cancer

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