Jab1 regulates HRR mRNA stability to modulate PARP inhibitor sensitivity in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype associated with the highest mortality rate among all breast cancer subtypes, primarily due to the absence of actionable therapeutic targets. Although poly (ADP-ribose) polymerase inhibitors (PARPi) have shown promising therapeutic effects in TNBC patients harboring homologous recombination deficiency (HRD), their clinical benefit remains limited, highlighting an urgent need for novel targets that enhance PARPi efficacy. This study investigates the role of Jab1 in regulating the stability of homologous recombination repair (HRR)-related RNAs and evaluates its potential as a therapeutic target to enhance PARPi sensitivity in TNBC.

Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair.

A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.

Background: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed.