Mechanisms of tumor cell resistance to the current targeted-therapy agents

Tumour Biol. 2016 Aug;37(8):10021-39. doi: 10.1007/s13277-016-5059-1. Epub 2016 May 7.

Abstract

Resistance to chemotherapy agents is a major challenge infront of cancer patient treatment and researchers. It is known that several factors, such as multidrug resistance proteins and ATP-binding cassette families, are cell membrane transporters that can efflux several substrates such as chemotherapy agents from the cell cytoplasm. To reduce the adverse effects of chemotherapy agents, various targeted-based cancer therapy (TBCT) agents have been developed. TBCT has revolutionized cancer treatment, and several agents have shown more specific effects on tumor cells than chemotherapies. Small molecule inhibitors and monoclonal antibodies are specific agents that mostly target tumor cells but have low side effects on normal cells. Although these agents have been very useful for cancer treatment, however, the presence of natural and acquired resistance has blunted the advantages of targeted therapies. Therefore, development of new options might be necessary. A better understanding of tumor cell resistance mechanisms to current treatment agents may provide an appropriate platform for developing and improving new treatment modalities. Therefore, in this review, different mechanisms of tumor cell resistance to chemotherapy drugs and current targeted therapies have been described.

Keywords: Chemotherapy; Drug resistance; Monoclonal antibodies; Small molecule inhibitors; Targeted-based cancer therapy; Tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis
  • Biotransformation / genetics
  • Chronopharmacokinetics
  • DNA Methylation
  • DNA Repair
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / physiology
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology*
  • Gene Amplification
  • Genes, MDR
  • Humans
  • Molecular Targeted Therapy
  • Multidrug Resistance-Associated Proteins / physiology
  • Mutation
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplastic Stem Cells / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • DNA Repair Enzymes