P2, N=56, Not yet recruiting, The Netherlands Cancer Institute

Docetaxel (DTX) remains a first-line treatment for advanced prostate cancer; however, its considerable side effects restrict therapeutic outcomes...Collectively, H-MnO2@IR825/DTX integrates TME remodeling with PTT, PDT, CDT, and chemotherapy, eliciting potent synergistic antitumor effects against prostate cancer through ROS-dependent apoptosis and pyroptosis, while exhibiting low toxicity to normal cells. This rationally designed nanoplatform represents a promising strategy for effective and safe prostate cancer therapy.

This novel dual mechanism-disrupting SAC assembly and nucleocytoplasmic transport-renders norlichexanthone a superior cytotoxic agent. Our findings position norlichexanthone as a promising chemotherapeutic candidate that promotes cancer cell death by targeting TPR-mediated pathways across both interphase and mitosis.

To determine combination partners that enhance RAS(ON) mutant-selective inhibition, a drug repurposing screen revealed that KRASG13C models are selectively vulnerable to chemotherapy. Combination of docetaxel with RMC-8839 demonstrated robust anti-proliferative activity in KRASG13C-driven NSCLC models in vitro and in vivo.

These findings identify a mechanistic axis in which docetaxel-induced tumor sensitization via TRAIL-R2 cooperates with Vβ-targeted T cell expansion to drive coordinated immune-mediated tumor regression. This work supports the clinical evaluation of STAR0602 in combination with chemotherapy and highlights TRAIL-R2-mediated tumor sensitization as a mechanistically defined strategy to enhance immunotherapy efficacy in immune-excluded tumors.

Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains clinically challenging due to tumor heterogeneity and resistance to standard microtubule-targeting agents, such as docetaxel and cabazitaxel. The top upregulated proteins, TTLL3, ANAPC7, PIK3CA, ARID4B, and COL16A1, are linked to microtubule dynamics and cell cycle regulation; the main downregulated, namely KDM2B, PTOV1, YWHAQ, PSMB6, and PRKCB, are involved in cell survival, protein homeostasis and mitotic checkpoint control. These findings provide proteomic evidence that (+)-PTC interferes with cytoskeletal protein dynamics and promotes apoptosis in mCRPC and so warranting its further investigation as a candidate anti-cancer scaffold.

This case suggests that disitamab vedotin combined with toripalimab may have activity in selected patients with advanced urothelial carcinoma, including those with low HER2 expression. However, the findings should be interpreted cautiously, and further studies are needed to clarify the role of this regimen and the value of predictive biomarkers.

In TRITON3, rucaparib improved radiographic progression-free survival (rPFS) over physician's choice of therapy (docetaxel or a second-generation androgen-receptor pathway inhibitor [ARPI]). For patients with BRCA mutations, rucaparib offers a targeted oral alternative to chemotherapy that can delay mCRPC progression while reducing many of the logistical, physical, and clinical burdens commonly associated with chemotherapy. Its oral administration and flexible dosing enable an individualized approach that reduces treatment interruptions and maximizes clinical benefits.

In PC-3 cells, upregulation of FOXO3 significantly inhibited vimentin expression and promoted E-cadherin expression, as well as enhanced cell sensitivity to docetaxel...Consistently, the in vivo experiments further confirmed the cancer inhibitory role of LINC00222 in prostate cancer. The present study revealed that LINC00222 adsorbed miR-19a to modulate FOXO3/APC/β-catenin signaling cascades and thereafter inhibited prostate cancer progression, which provided valuable insights into prostate cancer treatment.

Utidelone plus capecitabine has brought therapeutic and survival benefits in the second-line treatment of patients with advanced breast cancer (ABC). Utidelone demonstrates favorable efficacy and safety in patients with refractory ABC, particularly in HR+/HER2- patients. The combination of utidelone with anti-angiogenic therapy shows promising intracranial anti-tumor activity and is expected to be a preferred option for ABC in subsequent lines of treatment.

Three ADCs are currently approved for previously treated gynaecological cancers: mirvetuximab soravtansine for folate receptor-α-positive ovarian cancer, trastuzumab deruxtecan for solid tumours expressing HER2 (defined as a staining intensity on immunohistochemistry of 3+) and tisotumab vedotin for cervical cancer (independent of tissue factor expression). Moreover, rational combinations could reinforce and extend the clinical potential of these agents, as has already been demonstrated with the addition of ADCs to immune checkpoint inhibitors in an effort to amplify antitumour immunity and prolong the durability of clinical responses. In this Review, we provide an overview of the current landscape of ADCs in gynaecological malignancies, highlighting key advances and future opportunities.

P2/3, N=126, Not yet recruiting, AstraZeneca AB