Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer

Cancer J. May-Jun 2013;19(3):200-7. doi: 10.1097/PPO.0b013e318292e4e3.

Abstract

In recent years, there have been multiple breakthroughs in our understanding of lung cancer biology. Despite significant advances in molecular targeted therapies, DNA-damaging cytotoxic therapies will remain the mainstay of lung cancer management for the near future. Similar to the concept of personalized targeted therapies, there is mounting evidence that perturbations in DNA repair pathways are common in lung cancers, altering the resistance of the affected tumors to many chemotherapeutics as well as radiation. Defects in DNA repair may be due to a multitude of mechanisms including gene mutations, epigenetic events, and alterations in signal transduction pathways such as epidermal growth factor receptor and phosphoinositide 3-kinase/AKT. Functional biomarkers that assess the subcellular localization of central repair proteins in response to DNA damage may prove useful for individualization of cytotoxic therapies including poly(adenosine diphosphate-ribose) polymerase inhibitors. A better mechanistic understanding of cellular sensitivity and resistance to DNA damaging agents should facilitate the development of novel, individualized treatment approaches. Absolute resistance to radiation therapy, however, does not exist. To some extent, radiation therapy will always have to remain unselective and indiscriminant to eradicate persistent, drug-resistant tumor stem cell pools.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Hypoxia
  • Cell Proliferation
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Drug Resistance, Neoplasm*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy*
  • Radiation Tolerance*
  • Tumor Burden

Substances

  • Biomarkers, Tumor