Pharmacological inhibition of HSP90 and ras activity as a new strategy in the treatment of HNSCC

Journal of Cellular Physiology
Gabriella MissoMichele Caraglia

Abstract

Advanced head and neck squamous cell cancer (HNSCC) is currently treated with taxane-based chemotherapy. We have previously shown that docetaxel (DTX) induces a ras-dependent survival signal that can be antagonized by farnesyl transferase inhibitors (FTI) such as tipifarnib (TIP). Here we show that the synergistic TIP/DTX combination determines synergistic apoptotic conditions but, at the same time, it modulates the expression of the components of the multichaperone complex that is, in turn, involved in the regulation of the stability of members of the ras-mediated pathway. Therefore, we have stably transfected HNSCC KB and Hep-2 cells with a plasmid encoding for HSP90. The expression of the protein was increased in both transfected cell lines but its activation status was increased in Hep-2 clones and decreased in KB clones. On the basis of these results, we have treated both parental and HSP90-transfected cells with a HSP90 inhibitor geldanamycin (GA). We have found that the antiproliferative activity of GA is dependent upon the activation status of HSP90 and that it is strongly synergistic when added in combination with TIP but not with DTX in cells overexpressing HSP90 and even more in cells with increased HSP90 activity. T...Continue Reading

References

Jun 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R J BlackD M Parkin
Feb 12, 1998·Oral Oncology·S FranceschiR Talamini
Sep 29, 1999·Cancer Chemotherapy and Pharmacology·L G WangD R Budman
May 3, 2000·Lancet·J Crown, M O'Leary
Nov 4, 2000·The Journal of Cell Biology·H ZhouR N Pittman
Apr 3, 2001·International Journal of Cancer. Journal International Du Cancer·H MitsuiS Kimura
Jul 27, 2001·Journal of Cellular Physiology·K Richter, J Buchner
Oct 25, 2003·Oncogene·George A OrrSusan Band Horwitz
May 29, 2004·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hong Zhang, Francis Burrows
Mar 18, 2005·Cancer·Caroline H ShiboskiRichard C K Jordan
Jun 23, 2005·Frontiers in Bioscience : a Journal and Virtual Library·M CaragliaA Abbruzzese
Sep 23, 2006·International Journal of Cancer. Journal International Du Cancer·Lalle HammarstedtEva Munck-Wikland
Jan 30, 2007·Endocrine-related Cancer·Marissa V Powers, Paul Workman
Feb 22, 2008·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Oct 24, 2009·Cancer Letters·Yayoi FukuyoNobuo Horikoshi
Feb 9, 2011·Journal of Cellular Physiology·James A McCubreyAlberto M Martelli
Apr 6, 2011·Journal of Cellular Physiology·Santanu DasguptaPaul B Fisher
Jun 21, 2011·Journal of Cellular Physiology·Jarrett T WhelanMyon-Hee Lee
Dec 17, 2011·Indian Journal of Medical and Paediatric Oncology : Official Journal of Indian Society of Medical & Paediatric Oncology·Naresh SomaniH Singhal
Jan 19, 2012·Current Treatment Options in Oncology·Katharine A R Price, Ezra E Cohen

❮ Previous
Next ❯

Citations

Jul 11, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Ming-Shun WuYen-Chou Chen
Apr 29, 2016·American Journal of Clinical Pathology·Pablo ZoroquiainMiguel N Burnier
May 28, 2013·Journal of Amino Acids·Isabel Gomez-MonterreyPaola Stiuso
Aug 22, 2015·Acta otorrinolaringológica española·Jacinto García LorenzoMercedes Camacho Pérez de Madrid
Dec 17, 2014·International Journal of Oncology·Zuzana SolárováPeter Solár
Jun 4, 2019·Seminars in Cell & Developmental Biology·Marianna AbateGabriella Misso

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.