Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Echinobase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Echinobase
ECB-ART-50098
Cancer J 2013 Jan 01;193:238-46. doi: 10.1097/PPO.0b013e31829a68eb.
Show Gene links Show Anatomy links

Membrane phospholipids, EML4-ALK, and Hsp90 as novel targets in lung cancer treatment.

Laszlo A , Thotala D , Hallahan DE .


Abstract
Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease; combined cytotoxic chemotherapy and radiation therapy delivered concurrently has been established as the standard treatment for such patients. Despite many clinical trials that tested several different radiochemotherapy combinations, it seems that a plateau of efficiencies at the acceptable risk of complications has been reached. Clinical studies indicate that the improved efficacy of radiochemotherapy is associated with the radiosensitizing effects of chemotherapy. Improvement of outcomes of this combined modality by developing novel radiosensitizers is a viable therapeutic strategy. In addition to causing cell death, ionizing radiation also induces a many-faceted signaling response, which activates numerous prosurvival pathways that lead to enhanced proliferation in the endothelial cells and increased vascularization in tumors. Radiation at doses used in the clinic activates cytoplasmic phospholipase A2, leading to increased production of arachidonic acid and lysophosphatidylcholine. The former is the initial step in the generation of eicosanoids, while the later is the initial step in the formation of lysophosphatidic acid, leading to the activation of inflammatory pathways. The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) is member of the insulin superfamily of receptor tyrosine kinases. The EML4-ALK fusion gene appears unique to lung cancer and signals through extracellular signal regulated kinase and phosphoinositide 3-kinase. Heat shock protein 90 (Hsp90) is often overexpressed and present in an activated multichaperone complex in cancer cells, and it is now regarded as essential for malignant transformation and progression. In this review we focus on radiosensitizing strategies involving the targeting of membrane phospholipids, EML4-ALK, and Hsp90 with specific inhibitors and briefly discuss the combination of radiation with antivascular agents.

PubMed ID: 23708071
PMC ID: PMC3718064
Article link: Cancer J
Grant support: [+]


References [+] :
Acquaviva, Targeting KRAS-mutant non-small cell lung cancer with the Hsp90 inhibitor ganetespib. 2012, Pubmed