Heat shock protein (HSP) (HSP)

Heat shock proteins (HSPs) are a highly conserved family of molecular chaperones that play a critical role in maintaining protein homeostasis (proteostasis) by assisting in the folding, stabilization, and degradation of proteins (Source: UniProt, StatPearls). They are categorized by their molecular weight (e.g., HSP60, HSP70, HSP90) and are often upregulated in response to cellular stress such as heat, hypoxia, or malignancy (Source: PubMed, PMC4110032). In cancer, HSPs—particularly HSP90—are frequently overexpressed to stabilize mutated or overexpressed oncoproteins, thereby promoting tumor cell survival and proliferation (Source: NIH, PubChem). Consequently, HSPs have become significant therapeutic targets, with various small-molecule inhibitors developed to disrupt their ATPase activity and trigger the degradation of their client proteins (Source: Journal of Hematology & Oncology). Beyond oncology, HSPs are implicated in neurodegenerative diseases where they may prevent the aggregation of misfolded proteins like amyloid-beta or tau (Source: Nature Reviews Drug Discovery). Despite their therapeutic potential, clinical development has faced challenges including systemic toxicity and the induction of compensatory stress responses (Source: Clinical Cancer Research).

Other names

Molecular chaperoneStress proteinChaperonin

Inhibition of the ATPase activity of the chaperone, leading to the destabilization and subsequent proteasomal degradation of client proteins, many of which are oncogenic signaling proteins (Source: PubMed, PMC4110032).