ESMO Congress 2026

#AACR26 | ADC + #PARPi - finally a rational approach

Dr. Elizabeth Lee reviews gapped schedule olaparib plus DS-8201a (T-DXd) in HER2 expressing tumors, endometrial and ovarian cancers, ORR ...

Phase 1/2 Study Of PARP Inhibition With Olaparib To Enhance The Efficacy Of High-Dose Chemotherapy In Refractory And Relapsed Germ Cell Tumors

Drug: olaparib

Targeting Polθ Helicase with RP-3467: Preclinical Validation and Clinical Response in a gBRCA1 ovarian cancer patient with an acquired PARPi resistance mutation in TP53BP1

RP-3467, a selective small-molecule inhibitor of DNA polymerase theta, suppresses Polθ enzymatic activity, abrogates microhomology-mediated end joining, and induces synthetic lethality in homologous recombination-deficient models. Combined with PARP inhibitors olaparib or rucaparib, it produced sustained tumor regression across multiple xenograft and patient-derived xenograft models without added systemic toxicity. In a phase 1 trial (NCT06560632), a heavily pretreated germline BRCA1-mutant ovarian cancer patient with a TP53BP1 loss-of-function mutation achieved a confirmed partial response to RP-3467 plus olaparib by RECIST v1.1.

Targeting ribosome biogenesis sensitizes PARPi-resistant triple-negative breast cancer

Inhibiting ribosome biogenesis with BMH-21 resensitizes PARPi-resistant triple-negative breast cancer to olaparib. The drug combination was synergistic in 4 PARPi-resistant cell lines and in 3 BRCA wild-type TNBC cell lines with intrinsic PARPi resistance, but not in parental cells. In MDAMB231 cells, the combination increased γH2AX-positive cells up to 7.3-fold, SA-β-gal staining 5.6-fold and p21 3.6-fold, findings mirrored with CX-5461. Patient cohort data linked ribosomal pathway activity to MYC, proliferation, DNA damage and senescence.