Targeting the Proteasome Pathway for the Treatment of Solid Tumors

摘要: The ubiquitin-proteasome system (UPS) is a highly complex protein network that maintains proteostasis and cell viability through the targeted timely turnover of selected substrates. proteasome serves as catalytic core UPS to precisely recognize efficiently execute rapid ATP-dependent removal ubiquitinated proteins. Small-molecule pharmacologic inhibitors exploit pivotal role in cellular metabolism molecular vulnerability cancer cells promote selective cytotoxicity tumor cells. Proteasome (PIs) have yielded durable clinically responses dramatically improve survival patients diagnosed with invariably fatal hematologic malignancy multiple myeloma (MM). Success PI bortezomib treatment MM has emerged standard care catapulted into position prominence model biology drug development. However, advancement PIs solid tumors been far more challenging less successful. Clinical assessment second-generation progresses well pharmacologics intervene at other points within being explored for both tumors. Agents target non-proteolytic activities associated are emerging agents inhibit Ub-binding New approaches unravel should advance its utilization development platform mechanism-based anticancer strategies include monotherapy or synergistic combinations outcome