Targeting Proteostasis Pathways for Cancer Therapy

The critical role of protein disequilibrium in driving carcinogenesis has long been recognized. Though several inhibitors of heat shock protein (HSP) family members have entered clinical trials, none of them have been approved for clinical use as a result of inevitable toxicity, leading to the identification of safer therapeutic approaches sharing a similar efficacy relevant and urgent. Through delineating the role of HSP90 inhibitors in arresting cancer hallmarks, this paper identified HSP90 inhibition as an effective therapeutic strategy capable of concomitantly targeting multiple key transformed properties of cancers via modulating cellular proteostasis. Through interrogating intrinsic connections between proteostasis and redox homeostasis, this paper proposed cold atmospheric plasma (CAP) as a possible alternative of HSP90 inhibitors with little adverse effects. This paper extended the therapeutic spectrum of HSP90 inhibitors and CAP to inflammation-driven pathologies including autoimmune diseases, as inflammation is a manifestation of failed proteostasis. These insights may conceptually advance our understandings on the driving force of cancers that can be easily extended to other disorders originated from imbalanced proteostasis and abnormal inflammation. Tools proposed here for inhibiting HSP90 including CAP and its possible synergy with HSP90 inhibitors may shift the current treatment paradigm to a new avenue in oncology and other relevant fields.