Molecular Pathways: Increased Susceptibility to Infection Is a Complication of mTOR Inhibitor Use in Cancer Therapy

Clin Cancer Res. 2016 Jan 15;22(2):277-83. doi: 10.1158/1078-0432.CCR-14-3239. Epub 2015 Nov 25.


As one of the earliest examples of "chemical biology," the M: echanistic T: arget of R: apamycin (mTOR) protein and its chemical inhibitors have been extensively studied across a spectrum of physiologic and pathologic processes at the molecular, organismal, and patient population levels. There are several FDA-approved mTOR inhibitors (sirolimus, everolimus, and temsirolimus) with indications for cancer treatment and for prevention of solid organ rejection. Dozens of mTOR inhibitors are currently being evaluated in hundreds of ongoing clinical trials across a spectrum of diseases, including numerous cancer indications, autoimmune diseases, and a number of congenital disorders. As many of the approved and investigational indications for mTOR inhibitors require long-term treatment, the magnitude and incidence of particular side effects differ from those observed in shorter-term treatments. Here, we focus on the increased risk of infections in patients being treated with mTOR inhibitors. While increased infection rates might be expected from a class of drugs approved as posttransplant immunosuppressants, we review reports from clinical, mechanistic, and genetically engineered mouse model studies detailing a much more nuanced view of mTOR inhibitor drug action and target biology.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Communicable Diseases / etiology*
  • Disease Susceptibility / etiology*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Neoplasms / drug therapy
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*


  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases