Compared with chemotherapy with placebo, veliparib added to chemotherapy and continued as maintenance had significant patient-centered benefits in terms of quality-adjusted progression-free survival and on-treatment quality-adjusted time without symptoms of disease or toxicity for the overall, homologous recombination-deficient, and BRCA mutation patient populations.

Notably, albumin-bound paclitaxel and gemcitabine (AG) treatment induced the resistance to paclitaxel, accompanied by elevated KRAS and MAPK signaling, which was confirmed by transcriptomic comparison of PDAC patient samples with (30 cases) and without (60 cases) AG treatment. In a validation cohort of 29 organoids, pan-KRAS inhibitors exhibited superior efficacy against the residual organoids after AG treatment. These results provided insights into molecular changes in PDAC during treatment process and demonstrate that AG chemotherapy can activate the KRAS and MAPK signaling, presenting a potential target for therapeutic intervention.

Genetic knockdown or pharmacological inhibition of MCU disrupted GSH synthesis, suppressed stemness, and restored sensitivity to nab-paclitaxel plus gemcitabine (AG). High-throughput screening identified MCU inhibitor NB-598, which synergized with AG to inhibit tumor growth in preclinical models. These findings offer a potential novel therapeutic strategy to address chemoresistance in PDAC.

P2, N=66, Active, not recruiting, National Health Research Institutes, Taiwan | Trial primary completion date: Dec 2025 --> Dec 2027

P1, N=40, Completed, Beijing Wehand-Bio Pharmaceutical Co., Ltd | Not yet recruiting --> Completed

The combination of weekly dose-dense paclitaxel and pembrolizumab demonstrated promising activity and was well tolerated, although edema may be increased.

To address this challenge, we developed a nano-codelivery system, CGT-Cls-PTX/CM, for the co-delivery of paclitaxel (PTX) and tumor cell lysate-derived antigens from pancreatic cancer cells (from human pancreatic cancer PANC-1 and mouse pancreatic cancer PANC02 cells)...Overall, CGT-CLs-PTX/CM effectively remodels the immunosuppressive TME, achieving synergistic antitumor effects through combined chemotherapy and immune modulation. This strategy offers a promising approach for enhancing immunotherapeutic efficacy against pancreatic ductal adenocarcinoma, a prototypical "cold" tumor resistant to immune checkpoint therapy.

The control group received standard paclitaxel plus carboplatin (TP) chemotherapy (paclitaxel + carboplatin), while the treatment group received TP combined with Sanshen Fuzheng Decoction. No significant differences were observed in liver/kidney function, febrile neutropenia, or absolute neutrophil count (ANC) reduction (P > 0.05). San shen Fu zheng Decoction, as an adjunct to chemotherapy in ovarian cancer, showed potential benefits in improving hematological recovery, reducing rhG-CSF use, and alleviating treatment-related symptoms.

Together, our findings support a model in which dysregulated CRL3GMCL1-mediated degradation of 53BP1 prevents proper MSP function, leading to p53 degradation and continued proliferation. Targeting GMCL1 may, therefore, represent one possible avenue for addressing paclitaxel resistance in cancer cells with functional p53.

Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario. https://clinicaltrials.gov/study/NCT04675866?term=Hou%20Xinfang&rank=1, identifier NCT04675866.

Proteomic profiling of the TME further elucidates the heterogeneity of immunotherapy responses, offering insights for precision strategies in ESCC neoadjuvant therapy. Trial registration This study was prospectively registered in the Chinese Clinical Trial Registry (ChiCTR2000041081).