Targeting chromosomal instability in patients with cancer
Jul 11, 2024 · The development of synthetic lethal approaches in the context of CIN has led to the development of several novel treatment approaches, including KIF18A inhibitors, p53-reactivating agents and...
Mutant p53 gains oncogenic functions through a chromosomal
Jan 2, 2024 · Here, we study the mutp53 interactome and find that by targeting minichromosome maintenance complex components (MCMs), GOF mutp53 predisposes cells to replication stress and chromosomal instability...
p53 Is Not Required for High CIN to Induce Tumor Suppression
Jan 4, 2021 · Here, we test whether high CIN causes cell death and tumor suppression even in the absence p53. Despite a surprising sex-specific difference in tumor spectrum and latency in p53 heterozygous animals, these studies demonstrate that p53 is not required for high CIN to induce tumor suppression.
The emerging links between chromosomal instability (CIN), metastasis ...
May 14, 2019 · Aneuploidy is often caused by Chromosomal Instability (CIN), a process of continuous chromosome mis-segregation. CIN is believed to endow tumours with enhanced evolutionary capabilities due to increased intratumour heterogeneity, and facilitating adaptive resistance to therapies.
Targeting p53 pathways: mechanisms, structures and advances in …
Mar 1, 2023 · The p53 protein is a transcription factor that can activate the expression of multiple target genes and plays critical roles in regulating cell cycle, apoptosis, and genomic stability, and is...
The p53/p73 - p21CIP1 tumor suppressor axis guards against …
Nov 9, 2020 · As demonstrated here, functional inactivation of p53/p73 or loss of p21 CIP1 can drive CIN in a CDK1-dependent manner. Direct overexpression of CDK1 or of its activating subunit cyclin B (CNNB1/2) are obvious additional possibilities to …
The p53 Pathway: Origins, Inactivation in Cancer, and Emerging ...
Inactivation of the transcription factor p53, through either direct mutation or aberrations in one of its many regulatory pathways, is a hallmark of virtually every tumor.
The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor ...
p53-mediated premature senescence, which is a form of permanent cell-cycle arrest, is a potent antitumor mechanism in cells that are resistant to apoptosis. This effect was illustrated by blocking the apoptosis pathway in Myc-induced lymphoma with Bcl2.
Targeting mutant p53 for cancer therapy: direct and indirect strategies ...
Sep 28, 2021 · The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53.
Clinical Implications of Chromosomal Instability (CIN) and
Aug 1, 2019 · The action of p53 in protecting against aneuploidy stems from its activation in cells with numeric chromosomal aberrations (extra or missing chromosomes) . Activation of p53 is triggered in cells with chromosomal aberrations, and thus, p53 mutations are selected in …