Lynparza (olaparib)

PARP inhibitor (olaparib and niraparib) maintenance therapy yields favorable clinical outcomes for elderly ovarian cancer patients. Three clinical factors, attainment R0(no residual disease) after initial surgery, BRCA mutation, and CA-125 ≤10 U/mL before PARP inhibitor treatment, were predictive of longer PFS in elderly ovarian cancer patients undergoing first-line maintenance therapy with PARP inhibitors.

Autophagy inhibition downstream of the mTOR pathway is a mechanism of PARPi sensitivity in SCLC. This suggests that a therapeutic combination of autophagy inhibition and PARPi is a promising treatment strategy in SCLC, paving the way for the adoption of novel treatments in this disease context.

Agents such as olaparib, talazoparib, and niraparib have demonstrated promising efficacy in both neoadjuvant and adjuvant settings with some trials suggesting that selected patients may avoid chemotherapy. Overall, current evidence supports the role of HRD as a promising biomarker in TNBC. However, further research is required to refine its clinical utility and to integrate HRD testing into personalized treatment strategies, especially in combination with emerging therapies such as immunotherapy.

P1/2, N=1200, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P2, N=58, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Sep 2026 | Trial primary completion date: Mar 2025 --> Sep 2026

P2, N=333, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P2, N=71, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

Targeting this vulnerability, THOC2 knockdown induced synthetic lethality with PARPi, reducing Olaparib IC50 by up to 61% and suppressing tumor growth by 76% (P<0.001). Our study illuminates mRNA transport as a druggable DDR modulator and establishes THOC2 as both a prognostic biomarker and a therapeutic target to overcome PARPi resistance in HCC. This work pioneers a strategy to expand synthetic lethality beyond genetic defects by targeting post-transcriptional regulation.

P2, N=12, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | N=37 --> 12 | Trial primary completion date: Dec 2026 --> Jul 2026 | Recruiting --> Active, not recruiting

P3, N=110, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2026 --> Feb 2027

Mechanistically, 5i increases DNA damage by inhibiting SYK-mediated CtIP phosphorylation and shows synergy with the PARP inhibitor Olaparib. These findings establish 5i as a promising therapeutic candidate and demonstrate the potential of SYK inhibition as a strategy to overcome HR-mediated resistance in TNBC.

Molecular studies were performed in axitinib (VEGFR inhibitor)-treated human aortic endothelial cells, and vascular studies were undertaken in isolated intact vessels from mice...This was accompanied by increased p53 acetylation; these effects were mitigated by olaparib or the SIRT1 activator SRT1720...In conclusion, inhibition of VEGFR signalling induces oxidative stress and PARP activation, leading to SIRT1 downregulation, endothelial dysfunction and vascular inflammation. Targeting PARP activation or enhancing SIRT1 activity might represent promising strategies to mitigate VEGF inhibitor-induced vascular complications.