This review addresses the amyloid aggregation of pVHL, the factors contributing to this behavior, the correlation between protein aggregation and cellular dormancy, and potential therapeutic strategies that bridge protein aggregation and oncology.
Abstract
Protein aggregation is no longer viewed only as pathological but as a dynamic and reversible regulatory mechanism in cancer. Within the tumor microenvironment, proteins such as the von Hippel‐Lindau tumor suppressor protein (pVHL) can transition from a folded state to aggregated states. Mutations, environmental stress, and dysfunctional chaperone systems further promote pVHL aggregation. Structural plasticity enables adaptive responses that support protein storage, cell survival, and dormancy, a reversible state promoting drug resistance and cancer recurrence. Targeting protein aggregation with chemical chaperones and amyloid inhibitors could represent a promising therapeutic strategy to rescue the tumor suppressor activity and overcome dormancy‐associated drug resistance. In this review, we address the amyloid aggregation of pVHL, the factors contributing to this behavior, the correlation between protein aggregation and cellular dormancy, and potential therapeutic strategies that bridge protein aggregation and oncology.
The unfolded protein response (UPR) is a fundamental stress pathway coopted in cancer, and it is thought to drive adaptation, tumor progression, and therapeutic resistance. While the analysis of 'single-effector' biomarkers within the tumor microenvironment often fails to capture its spatial, temporal, and cellular com...
Quentin Bourgery, D. Doultsinos, A. Galmiche et al.· Trends in Molecular Medicine· 0 citations
Although preclinical studies have validated ASF1A as a promising prognostic biomarker and therapeutic target, relevant clinical trials supporting its clinical application remain absent.
Jun Yin, Xiao-Jian Zhuo, Li-Hui Wen et al.· Experimental and Therapeutic...· 0 citations
This Review examines the molecular engineering principles of bifunctional degraders and summarizes clinical progress demonstrating synergy with immune checkpoint blockade and adoptive cell therapy, and discusses how catalytic protein elimination overcomes primary immune evasion and adaptive resistance driven by compens...
Fu-Rong Zhang, Qian-Heng Wang, Ming-Xuan Li et al.· Frontiers in Immunology· 0 citations
Malignant tumor evolution is governed by its symbiotic relationship with the tumor microenvironment, which features steep oxygen and acidity gradients that drive malignant progression. Traditional biochemical frameworks fail to adequately explain the rapid, coordinated genomic alterations under such stresses. This revi...
Xing-Jian Luo· International Journal of Bio...· 0 citations
Mutations in TP53, the most frequently altered gene in human cancer, have long been interpreted within a genetic framework centered on loss of tumor-suppressive function and dominant-negative inhibition. Here, we highlight an emerging paradigm in which mutant p53 operates as a protein conformational disease. A growing...
Protein aggregation has traditionally been considered a hallmark of proteostasis disruption and cellular dysfunction. However, recent studies have revealed that bacterial protein aggregation is not merely a passive consequence of stress-induced damage but may represent a dynamic component of cellular adaptation. Under...
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.
