Background: Protein homeostasis (proteostasis) is vital for the survival of cells in physiological
and pathological conditions. Particularly, cancer cells are in constant state of cellular stress due to
rapid proliferation and decreased quality control in proteosynthesis and therefore, are exceedingly dependent
on the homeostasis pathways. Among the complex biological mechanisms regulating proteostasis
are the highly conserved molecular chaperones, heat shock proteins (HSPs). HSPs assist cell survival by
catalysing the proper folding of proteins, modulation of the apoptotic machinery and finally regulating the
protein degradation machinery, providing either the stability or the degradation of selected proteins under
stress conditions. Inevitably, HSPs are upregulated in malignancies and participate in different hallmarks
of cancer, with indispensable roles in the onset and progression of the disease. Moreover, high levels of
HSPs contribute to poor prognosis and treatment resistance in various cancers. Therefore these molecular
chaperones present as attractive targets for anti-cancer therapy.
Objective: This review describes how HSPs regulate different hallmarks of cancer and provides an overview
on the most relevant patents which have recently appeared in the literature.
Methods: The patents were extracted from Google Patents (2012-2016) while the clinical trial results
were mined from www.clinicaltrial.gov.
Results and Conclusion: Review of literature shows that the proteostatic functions of HSPs can modify
different hallmarks of cancer. Moreover, targeting HSPs (notably HSP27, HSP70 and HSP90) exhibited
positive results in clinical trials so far. However, more studies should be designed to optimize the efficacy
of mono or combination therapy in various malignancies.