It enhanced lymphocyte infiltration into tumors and modulated IFN-γ signaling pathways. These findings indicate that compound K-38 is a potent small molecule inhibitor of PTPN2, laying the groundwork for the future development of PTPN2-targeted therapeutics.

In B16-OVA syngeneic models, WS35 monotherapy and its combination with an anti-PD-1 antibody achieved robust tumor growth suppression, outperforming AC484, with no observable systemic toxicity. Collectively, WS35 represents a preclinical candidate with validated efficacy and safety for developing novel antimelanoma therapeutics.

P1, N=101, Completed, AbbVie | Active, not recruiting --> Completed

P1, N=101, Active, not recruiting, AbbVie | Trial completion date: May 2026 --> Aug 2025 | Trial primary completion date: May 2026 --> Aug 2025

Interestingly, TFRC is directly regulated by the transcription factor hypoxia-inducible factor 1 alpha (HIF1A) in its promoter. Notably, an orally bioavailable potent PTPN2/N1 active-site inhibitor ABBV-CLS-484 (AC484) demonstrates significant therapeutic potential against ALK+ ALCL by disturbing mitochondrial renewal and blocking TFRC-mediated PINK1-PRKN-dependent mitophagy to exert anti-tumor activities, providing critical insights into the selection of targeted treatment strategies for ALK+ ALCL patients and a strong rationale for advancing AC484 into clinical trials.

Key findings reveal that elevated PTPN21 levels hinder the apoptosis of ALL cells in response to vincristine (VCR) and daunorubicin (DNR). Restoring GADD45A reverses the anti-apoptotic effect of PTPN21. These findings suggest that targeting PTPN21 in conjunction with chemotherapy may represent a novel therapeutic strategy for ALL, offering potential implications for improving treatment efficacy and overcoming drug resistance.

P1, N=248, Recruiting, AbbVie | Trial primary completion date: Aug 2025 --> Oct 2026

This review outlines the structural modification processes of PTPN2-targeted agents, focusing primarily on inhibitors and degraders. Finally, this review endeavors to provide a comprehensive perspective on the evolving field of PTPN2-targeted drug discovery for tumor immunotherapy, offering valuable insights for future drug development.

P1, N=49, Active, not recruiting, Enterin Inc. | Recruiting --> Active, not recruiting

G. calidophilum has the potential to be developed into functional foods or drugs with the aim of preventing and treating cancer.

P1; Recruiting --> Active, not recruiting | N=263 --> 101 | Trial primary completion date: Aug 2025 --> May 2026

The triple therapy also resulted in a decrease in PD‑L1, PTP1B and TNFR2 expression within NSCLC tumor tissues in mice. Overall, the triple therapy effectively suppressed tumor growth and improved outcomes in mice with NSCLC by modulating immune cell distribution and reducing levels of target immune proteins.