HRD

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

Advances in molecular understanding and diagnostics are beginning to inform the development of targeted therapies. Future work may benefit from integrating cancer neuroscience with computational modelling, standardise diagnostic platforms, and test the survival impact of receptor reassessment in prospective trials.

In the PSM sensitivity analysis, the median PFS was not reached (95% CI, 19.55-NR) in the niraparib group and was 18.33 months (95% CI, 8.90-25.26) in the bevacizumab group (HR = 0.360, 95% CI, 0.176-0.736; P = .005).ConclusionThis analysis suggests that niraparib may provide a progression-free survival advantage compared with bevacizumab in BRCAwt AOC patients, with both regimens appearing to be generally well tolerated in the real-world setting. These findings offer preliminary reference value for maintenance treatment selection in patients with newly diagnosed BRCAwt AOC.

We propose that future trials involving women with premenopausal ER-positive disease must prioritize biology over age in defining eligibility, incorporate OFS as a SOC in the control arm and expand biomarker-driven approaches to refine both treatment escalation and de-escalation. A genomically and immunologically informed strategy is essential to improve the outcomes in this under-represented population.

Alterations in the homologous recombination (HR) DNA repair pathway are reported in 3.0-19.5% of PDAC patients. These types of alterations can sensitize tumors to platinum-based chemotherapy in PDAC as well as other cancers including ovarian, colorectal, and prostate cancers. Retrospective and prospective studies in locally advanced/metastatic PDAC demonstrate higher response rates and longer survival outcomes among HR-deficient (HRD) patients receiving platinum-based chemotherapy. A growing body of evidence in the neoadjuvant setting suggests a potential benefit for HRD-PDAC patients in terms of enhanced tumor downstaging, higher resectability, and improved survival outcomes compared with HR-proficient patients. However, prospective ad hoc studies are still warranted to confirm these findings Homologous recombination deficiency represents a promising biomarker to guide patient selection for neoadjuvant platinum-based chemotherapy in PDAC. Incorporation of HR deficiency-testing into neoadjuvant treatment schemes will enable a more personalized therapeutic approach, supporting the implementation of precision oncology for early-stage PDAC patients.

For these advanced diseases, the two main questions for surgical strategy are the feasibility of complete resection (without residual disease, CC-0), assessed during surgical exploration of pelvis and abdomen, and the optimal timing of this surgery (upfront or after neoadjuvant chemotherapy). In recurrent diseases, surgery remains a main piece of treatment in case of late relapse and medical treatment depends on drugs used in the first line; in early platinum resistant relapse, a new therapeutic option is available with mirvétuximab soravtansine.

P=N/A, N=60, Recruiting, Sun Yat-sen University Cancer Center (Sun Yat-sen University Cancer Hospital, Sun Yat-sen University Cancer Research Institute); Sun Yat-sen Universit

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.

In conclusion, dPathHRD offers a promising, cost-effective alternative to molecular testing, leveraging widely available digital pathology images to inform personalized treatment strategies. Further prospective validation is warranted to confirm its clinical applicability and predictive power.

These findings uncover a previously unrecognized CK2-HDAC5-Ku70 signaling axis that governs DNA repair pathway choice by regulating DNA end resection. Targeting this axis provides a mechanistic rationale for enhancing PARP inhibitor sensitivity in PDAC, including tumors without classical homologous recombination deficiency.

P3, N=200, Active, not recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University