Evolutionary dynamics of cancer in response to targeted combination therapy

In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden,…

• JT
  John Templeton Foundation
• MR
  Microsoft Research
• VA
  Virginia and D.K. Ludwig Fund for Cancer Research
• AS
  Austrian Science Fund

  Award: S11407-N23, P23499-N23
• NI
  National Institutes of Health

  Award: CA129825, CA43460, CA57345
• ER
  European Research Council

  Award: 279307
• NC
  National Cancer Institute

  Award: contract N01-CN-43309