BRCA mutation

No significant difference in follicular density was observed between women with BRCA1/BRCA2 mutations and those without. Our findings suggest that the presence of a BRCA mutation does not have a significant negative clinical impact on the follicular population of the ovarian cortex. Larger studies are needed to further validate these findings.

P2, N=14, Completed, Yuan Yuan | Active, not recruiting --> Completed | Trial completion date: Aug 2026 --> Nov 2025

P1/2, N=210, Recruiting, Shanghai SciBrunch Therapeutics Co., Ltd. | Not yet recruiting --> Recruiting

From a translational perspective, multiple clinical trials have confirmed the safety and preliminary efficacy of this combination strategy in solid tumors, particularly demonstrating synergistic antitumor activity in settings of PARPi resistance or in tumors with intact HRR function. The combinatorial approach of CDKi and PARPi, through multi-dimensional mechanistic integration, holds strong potential as a key strategy to overcome PARPi resistance and expand the population of patients who can benefit from this class of therapies.

In addition, the therapeutic landscape is rapidly changing, with new biomarker-driven studies targeting genotype (e.g., BRCA or PTEN mutant) and phenotype (e.g., prostate-specific membrane antigen status) in development for mHSPC. A better understanding of tumor heterogeneity, clonal evolution, and metastatic homing in prostate cancer will hopefully inform future strategies for local and systemic disease control, personalized monitoring strategies, and improved patient outcomes.

However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches...The model demonstrated high sensitivity to cisplatin plus gemcitabine, but limited efficacy of PARPi monotherapy...The addition of anti-PD1 treatment to PARPi maintenance enhanced tumor regression and prolonged overall survival. These findings provide preclinical support for ongoing clinical trials investigating immunotherapy with PARPi as a maintenance strategy in homologous recombination-deficient PDAC.

P=N/A, N=80, Not yet recruiting, Linyi Tumor Hospital; Linyi Tumor Hospital

Initial the standard of care (SOC) treatment includes intensive cytoreductive surgery (CRS) and platinum-paclitaxel chemotherapy with/without adding anti-angiogenetic agent and/or following poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) maintenance therapy based on biomarker-guided recommendation, such as BRCA mutation and/or homologous recombination deficiency (HRD significance)...Chemoresistance may be derived from "naïve" (underlying or primary) hereditary or acquired adaption (secondary or induced), which are involved in an increasing ability to self-repairing DNA, dysregulated autophagy process and evasion of apoptosis and alternation in mitochondrial pathways as well as metabolic adaptions, changing signaling pathway for proliferation and survival, and modifying genetic and epigenetic resolution, contributing to sustaining proliferative signaling, resisting cell death, evading growth suppressor, inducing angiogenesis, activating invasion and metastases, deregulating cellular energetics, reaching cellular senescence and stemness, and epigenetic reprogramming of cancer cells. The first part is a brief review for PR-rOC, including mechanisms, and combating strategies but only limited to cytoreductive surgery for treating PR-rOC patients.

Our novel classification revealed that PARPi efficacy and prognosis varied significantly by mutation location, with the central region linked to superior outcomes compared with the N- and C-terminal regions. Comprehensive mutation profiling should guide treatment decisions to optimize outcomes in patients with BRCA-mutated ovarian cancer.

Olaparib is active in pts with MBC with gPALB2m and sBRCAm, significantly expanding the population of pts with breast cancer likely to benefit from PARP inhibitors beyond gBRCA1/2m carriers.