Ferroptosis inducers (sorafenib, erastin) heightened LDH release and reduced viability, while inhibitors (ferrostatin-1, U0126) had opposing effects...STXBP1 functions as a tumor suppressor in glioma, regulating ferroptosis and EMT. It shows potential as a therapeutic target in glioma management.

Drug sensitivity prediction suggested differential therapeutic vulnerabilities, with high-risk patients showing increased predicted sensitivity to JAK inhibitors, dasatinib, and nutlin-3a. An LLPS-related three-gene RiskScore identifies GC subgroups with different prognosis, immune features, and therapeutic sensitivity.

Multi-target agents are no longer constrained by single-target effects; however, issues of balanced potency, ADMET, and control still exist. The combination of AI, quantum computing, and precision polypharmacology may enable more effective multi-target interventions to address unmet demands in complex diseases.

These findings suggest that ALDH1L2 contributes to reduced sunitinib sensitivity in RCC organoids by attenuating ferroptosis-related responses. HA-1 may improve the response of RCC organoids to sunitinib by targeting ALDH1L2, supporting further evaluation of this combination strategy.

This research pioneers the identification of anlotinib as an ER stress- and autophagy-dependent ICD inducer in HCC. Our comprehensive mechanistic dissection and robust preclinical evidence establish anlotinib's ability to convert immunologically "cold" tumors to "hot" ones through the FGFR-1/ER stress/autophagy/DAMP release axis. The synergy with anti-PD-1 and enhancement by metformin provide a rationale for novel combination strategies to overcome current limitations of targeted-immunotherapy, offering a promising approach to improve response rates in advanced HCC.

P1, N=30, Recruiting, Mayo Clinic | N=10 --> 30

P2/3, N=140, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Mar 2026

EV-derived miR-941 as a key driver of anlotinib resistance via the Keap1/Nrf2 pathway represent a promising non-invasive predictive biomarker and a potential therapeutic target for overcoming resistance in NSCLC.

Peroxisomes act as pivotal regulators of digestive cancer progression by modulating signaling pathways, the TIME, therapeutic resistance, and lipid metabolism. Targeting peroxisomal function, particularly in high-risk subgroups of HCC and CRC, warrants further exploration as a promising therapeutic strategy.

P1/2, N=73, Active, not recruiting, University of Southern California | Trial completion date: Jun 2026 --> Dec 2027

P2, N=0, Withdrawn, University of Miami | N=30 --> 0 | Recruiting --> Withdrawn

P2, N=34, Recruiting, Qilu Hospital of Shandong University | Not yet recruiting --> Recruiting