Focus V (anlotinib)

P2, N=48, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=29, Completed, Guangdong Provincial People's Hospital | Active, not recruiting --> Completed

Consistently, SOD2 knockout xenograft models exhibited enhanced antitumor responsiveness to TKIs in vivo. Collectively, these findings identified SOD2 as a key regulator of mitochondrial redox homeostasis and mitophagy, thereby modulating therapeutic sensitivity in HNSCC, and suggest that targeting the SOD2-superoxide metabolic axis may represent a promising strategy to improve TKIs efficacy in HNSCC.

Multiple chemotherapy regimens (ifosfamide, carboplatin, and etoposide; and doxorubicin, vincristine, cyclophosphamide, and cisplatin) demonstrated limited efficacy. Subsequent treatment with alternating albumin-paclitaxel, gemcitabine, ifosfamide, and etoposide/cyclophosphamide, irinotecan, and vincristine chemotherapy combined with anlotinib and cranial radiotherapy achieved disease stabilization, with no subsequent progression observed during follow-up. This case highlights the aggressive nature and chemoresistance of the mesenchymal components of HB, emphasizing the need for novel therapeutic approaches that incorporate targeted agents.

P2, N=33, Not yet recruiting, Sichuan University

The combination of tislelizumab and anlotinib demonstrated promising antitumor activity with a manageable safety profile as first-line therapy in patients with advanced PSC.

P2, N=40, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

This real-world case series suggests that sintilimab plus anlotinib offers promising efficacy and manageable toxicity as a later-line, chemotherapy-free regimen for advanced KRAS-mutant NSCLC. The absence of prior anti-angiogenic therapy emerged as a strong positive predictor for survival, underscoring the importance of strategic treatment sequencing in clinical practice.

Notably, while ferroptosis represents a key mechanism, STAT3 may also contribute to anlotinib resistance through additional pathways including apoptosis, autophagy, and immune evasion, reflecting the multifunctional role of this central signaling hub. Our results delineate a novel mechanism wherein METTL3 governs ferroptosis and anlotinib resistance in osteosarcoma through dual m6A methylation of circFAM120B and pri-miR-330, offering potential targets for overcoming therapeutic resistance.

Importantly, combined treatment with panobinostat and the anti-angiogenic agent anlotinib resulted in superior inhibition of tumor growth and vascularization compared with either monotherapy in patient-derived organoid xenograft models. Together, these findings uncover an enzymatic activity-independent RNA regulatory function of NQO1 in ESCC and provide a mechanistic rationale for targeting the NQO1/AGRN axis.

P2, N=27, Not yet recruiting, Fujian Cancer Hospital

Benmelstobart plus anlotinib showed longer progression-free survival than pembrolizumab plus placebo and no unexpected safety signals were reported, suggesting benmelstobart plus anlotinib as a potential first-line option in driver gene-negative, PD-L1-positive, advanced NSCLC. Longer term follow-up is needed to establish effects on overall survival.