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Heat shock protein 90 inhibitors in non-small-cell lung cancer

Pillai, Rathi N.; Ramalingam, Suresh S.

doi: 10.1097/CCO.0000000000000047
LUNG AND MEDIASTINUM: Edited by Robert Pirker

Purpose of review Heat shock protein 90 (Hsp90) protects cellular proteins from degradation by the ubiquitin-proteasome system in conditions of stress. Many cancers have increased expression of Hsp90 to ensure their malignant phenotype of increased proliferation, decreased apoptosis, and metastatic potential by conservation of proteins like epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, anaplastic lymphoma kinase (ALK), v-Raf murine sarcoma viral oncogene homologue B1, AKT, B-cell lymphoma 2, and cell cycle proteins. This review discusses recent developments in the strategy of Hsp90 inhibition as a targeted therapy in non-small-cell lung cancer (NSCLC).

Recent findings Hsp90 inhibitors result in growth inhibition and tumor regression in NSCLC cell lines and tumor xenograft models, both as monotherapy and in combination with other drugs. Hsp90 inhibition has particular efficacy in molecular subtypes of NSCLC, such as EGFR-mutated and ALK-rearranged NSCLC. IPI-504 and ganetespib have activity in NSCLC both as monotherapy and in combination with docetaxel.

Summary Preclinical studies and early clinical trials have confirmed the efficacy of Hsp90 inhibition as a targeted therapy in NSCLC. Ongoing trials will further define the utility of Hsp90 inhibitors in NSCLC.

Winship Cancer Institute, Emory University, Atlanta, Georgia, USA

Correspondence to Suresh S. Ramalingam, Professor, Director of Medical Oncology, 1365 Clifton Road NE, Rm C-3090, Atlanta, GA 30322, USA. Tel: +1 404 778 5378; fax: +1 404 778 5520; e-mail: suresh.ramalingam@emory.edu

© 2014 Lippincott Williams & Wilkins, Inc.