Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins Journal Article
| Authors: | Didelot, C.; Lanneau, D.; Brunet, M.; Joly, A. L.; De Thonel, A.; Chiosis, G.; Garrido, C. |
| Article Title: | Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins |
| Abstract: | Stress or heat shock proteins (Hsps) Hsp90, Hsp70 and Hsp27 are chaperones that assist the proteins in their folding, stability, assembly into multi-protein complexes and transport across cellular membranes. The expression of some of them is highly induced in response to a wide variety of physiological and environmental insults. Hsps have a dual function depending on their intracellular or extracellular location. Intracellular Hsps have a protective function. They allow the cells to survive to lethal conditions. The cytoprotective functions of Hsps can largely explain by their anti-apoptotic properties. Hsp90, Hsp70 and Hsp27 can directly interact with different proteins of the tightly regulated programmed cell death machinery and thereby block the apoptotic process at distinct key points. In cancer cells, where the expression of Hsp27, Hsp70 and/or Hsp90 is frequently abnorrnally high, they participate in oncogenesis and in resistance to chemotherapy. Therefore, the inhibition of Hsps has become an interesting strategy in cancer therapy. In contrast to intracellular Hsps, extracellular located or membrane-bound Hsps mediate immunological functions. They can elicit an immune response modulated either by the adaptive or innate immune system. In cancer, most immunotherapeutical approaches based on extracellular Hsps exploit their carrier function for immunogenic peptides. This review will discuss this different and often paradoxical approaches in cancer therapy based on the dual role of Hsps, protective/ tumorigenic versus immunogenic. © 2007 Bentham Science Publishers Ltd. |
| Keywords: | protein expression; leukemia; unclassified drug; clinical trial; review; cancer growth; drug potentiation; monotherapy; nonhuman; solid tumor; antineoplastic agents; drug targeting; antineoplastic agent; protein function; protein localization; neoplasms; cell survival; complex formation; gastrointestinal stromal tumor; imatinib; unindexed drug; cancer immunotherapy; melanoma; apoptosis; bortezomib; multiple myeloma; breast cancer; protein assembly; protein protein interaction; lung non small cell cancer; protein stability; antineoplastic activity; drug structure; drug screening assays, antitumor; tumor cells, cultured; structure activity relation; cancer therapy; carcinogenesis; cancer resistance; immune response; immunogenicity; cancer cell; protein transport; lymphoma; protein induction; 17 demethoxy 17 (2 dimethylaminoethylamino)geldanamycin; heat shock protein 90 inhibitor; tanespimycin; heat shock protein 90; innate immunity; immunomodulation; heat shock protein 27; heat shock protein 70; protein folding; trastuzumab; adaptive immunity; environmental factor; cell protection; protein inhibitor; heat shock proteins; cell membrane transport; tanespimycin hydroquinone; geldanamycin; radicicol; 3 (5 chloro 2,4 dihydroxyphenyl) n ethyl 4 (4 methoxyphenyl) 5 pyrazolecarboxamide; 4 [4 (1,4 benzodioxan 6 yl) 5 methyl 1h pyrazol 3 yl] 6 ethylresorcinol; kos 1022; ver 50589; multiprotein complex; snx 5422; heat-shock proteins; alvespimycin; kf 58333; novobiocin; cnf 1010; sta 9090; cancer cell growth; cancer cell resistance; coumamycin a1; shepherdin |
| Journal Title: | Current Medicinal Chemistry |
| Volume: | 14 |
| Issue: | 27 |
| ISSN: | 0929-8673 |
| Publisher: | Bentham Science Publishers |
| Date Published: | 2007-11-01 |
| Start Page: | 2839 |
| End Page: | 2847 |
| Language: | English |
| DOI: | 10.2174/092986707782360079 |
| PUBMED: | 18045130 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 37" - "Export Date: 17 November 2011" - "CODEN: CMCHE" - "Source: Scopus" |
