Six prognostic genes, particularly RAB25 and PLAU, influence ESCC progression and immune microenvironment remodeling.

P=N/A, N=100, Not yet recruiting, PETHEMA Foundation

P2, N=28, Recruiting, Mayo Clinic | Trial completion date: Nov 2026 --> Jun 2028 | Trial primary completion date: Nov 2026 --> Jun 2028

DS-8201 demonstrates potential as one of the effective salvage therapies following RC48 failure in HER2 altered solid tumors, showing significantly better disease control and a distinct, manageable toxicity profile. These findings highlight the importance of selecting personalized ADCs based on molecular subtypes and toxicity factors and provide a basis for future, larger-scale prospective studies.

P=N/A, N=701, Completed, Assistance Publique - Hôpitaux de Paris

A 64-year-old man with metachronous metastatic urothelial carcinoma originating from the right renal pelvis underwent nectin-4-targeted [68Ga]Ga-NECT-224 PET/CT prior to initiation of nectin-4-targeted antibody-drug conjugate (ADC) therapy with enfortumab-vedotin (PADCEV), in combination with pembrolizumab. Subsequent [68Ga]Ga-NECT-224 PET/CT restaging revealed multiple new lesions with intense nectin-4 expression. This case illustrates the potential of [68Ga]Ga-NECT-224 PET/CT to visualize heterogeneous nectin-4 expression, its potential in therapy guidance, and highlights the need for theranostic strategies in patients retaining target expression despite cytotoxic therapy resistance.

POLA demonstrated robust single-agent antitumor activity in vivo, including in PDX models derived from patients with ibrutinib-resistant MCL. This signature likely reflects core pathways associated with POLA resistance and highlights potential novel therapeutic vulnerabilities. These findings strongly support further clinical investigation of POLA in combination with VEN as a BCL2- and MCL1-targeting therapeutic strategy in patients with R/R MCL and BCL2-positive R/R DLBCL.

P2, N=102, Recruiting, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Knockdown of IGFL2 resensitizes resistant cells to DTX both in vitro and in mouse xenograft models. These findings establish IGFL2 as a regulator of DTX resistance via TLR4 signaling, suggesting its relevance as a therapeutic target for overcoming chemoresistance in GC.

These bidirectional changes indicate a metabolic coupling between tumor and circulation, driven by differential utilization and excretion processes during T-DM1 response. Collectively, our findings demonstrate that T-DM1 elicits coordinated local and systemic metabolic reprogramming, providing mechanistic insights into its antitumor activity and the metabolic coupling between tumor and circulation.

P=N/A, N=40, Not yet recruiting, University of Florence

In the real-world setting, RC48 shows some clinical efficacy and a manageable safety profile in patients with HER2-expressing advanced gastric cancer. These findings provide useful information for clinical practice.