Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors

• Published in: International journal of molecular sciences Vol. 20; no. 21; p. 5284
• Main Authors: Shevtsov, Maxim, Multhoff, Gabriele, Mikhaylova, Elena, Shibata, Atsushi, Guzhova, Irina, Margulis, Boris
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.10.2019; MDPI
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Apoptosis; Autophagy; Cancer; Cancer therapies; cancer therapy; Cell growth; Chaperones; Clinical trials; concurrent therapy; Drug delivery; Drug Therapy, Combination; Drugs; Gene expression; heat shock protein inhibitors; Heat shock proteins; Heat-Shock Proteins - antagonists & inhibitors; Heat-Shock Proteins - metabolism; hsp27; Hsp27 protein; hsp70; HSP70 Heat-Shock Proteins - antagonists & inhibitors; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; hsp90; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - metabolism; Hsp90 protein; Humans; Hyperthermia; Inhibitors; Isoxazoles - chemistry; Isoxazoles - therapeutic use; Kinases; Lung cancer; Medical research; Melanoma; Metastasis; molecular chaperones; Molecular Chaperones - antagonists & inhibitors; Molecular Chaperones - metabolism; Monoclonal antibodies; Nanoparticles; Neoplasms - drug therapy; Oligonucleotides - chemistry; Oligonucleotides - therapeutic use; Oxidative stress; Pancreatic cancer; Peptides; Phosphorylation; Physiology; Prostate cancer; Radiation; Resorcinols - chemistry; Resorcinols - therapeutic use; Review; RNA polymerase; Tumors; HSP90; cancer therapy; HSP70; HSP27; concurrent therapy; molecular chaperones; heat shock protein inhibitors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20215284

Most molecular chaperones belonging to heat shock protein (HSP) families are known to protect cancer cells from pathologic, environmental and pharmacological stress factors and thereby can hamper anti-cancer therapies. In this review, we present data on inhibitors of the heat shock response (particularly mediated by the chaperones HSP90, HSP70, and HSP27) either as a single treatment or in combination with currently available anti-cancer therapeutic approaches. An overview of the current literature reveals that the co-administration of chaperone inhibitors and targeting drugs results in proteotoxic stress and violates the tumor cell physiology. An optimal drug combination should simultaneously target cytoprotective mechanisms and trigger the imbalance of the tumor cell physiology.