Resistance to chemotherapy and molecularly targeted therapies: rationale for combination therapy in malignant melanoma

Curr Mol Med. 2011 Oct;11(7):553-63. doi: 10.2174/156652411800615153.


Metastatic melanoma is one of the most intractable tumors, with all current regimens showing limited survival impact. Failure of most agents is attributed to development of therapy resistance. Accumulated evidence points to the apoptotic defect of melanoma cells and the surge of survival signals stimulated by cytotoxic drugs, as a way that tumors circumvent cytotoxic chemotherapy. An overview of inhibitors developed against these growth/survival factors, which are potential partners to be combined with systemic chemotherapy, will be discussed. The escape mechanism from molecular inhibitors also suggests a "vertical" or "horizontal" combination of molecularly targeted therapies. A better understanding of the interactions between simultaneously used regimens and of the rationale for combination therapy will provide new insights to improve survival and quality of life in patients with advanced melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm*
  • Humans
  • Melanoma / drug therapy*
  • Models, Biological
  • Molecular Targeted Therapy
  • Skin Neoplasms / drug therapy*


  • Angiogenesis Inhibitors
  • Antineoplastic Agents