mTOR Signaling Confers Resistance to Targeted Cancer Drugs

Trends Cancer. 2016 Nov;2(11):688-697. doi: 10.1016/j.trecan.2016.10.006. Epub 2016 Nov 4.


Cancer is a complex disease and a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, the clinical benefits of such drugs are at best transient due to tumors displaying intrinsic or adaptive resistance. The underlying compensatory pathways that allow cancer cells to circumvent a drug blockade are poorly understood. We review here recent studies suggesting that mammalian TOR (mTOR) signaling is a major compensatory pathway conferring resistance to many cancer drugs. mTOR-mediated resistance can be cell-autonomous or non-cell-autonomous. These findings suggest that mTOR signaling should be monitored routinely in tumors and that an mTOR inhibitor should be considered as a co-therapy.

Keywords: adaptive resistance; rapamycin; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*


  • Antineoplastic Agents
  • TOR Serine-Threonine Kinases