Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.

Hypoxia afflicts the microenvironment of solid tumors fueling malignancy. We investigated the impact of long hypoxia exposure on transcriptional remodeling, tumor mutational burden (TMB), and genomic instability of cancer cells that were grouped based on their inherent sensitivity or resistance to hypoxia. A hypoxia score was used as a metric to distinguish between the most hypoxia-sensitive (hypoxia high (HH)), and most resistant (hypoxia low (HL)) cancer cells.

p53 reactivating small molecule PRIMA‑1/APR‑246 regulates genomic instability in MDA‑MB‑231 cells.

Pharmacological reactivation of tumor‑suppressor protein p53 has acted as a promising strategy for more than 50% of human cancers that carry a non‑functional mutant p53 (mutp53). plays a critical role in preserving genomic integrity and DNA fidelity through numerous biological processes, including cell cycle arrest, DNA repair, senescence and apoptosis. By contrast, non‑functional mutp53 compromises the aforementioned genome stabilizing mechanisms through gain of function, thereby increasing genomic instability in human cancers.