CLDN6 (Claudin 6)

CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC, suggesting its utility as a prognostic biomarker and potential therapeutic target.

CLDN6, CLDN9, and CLDN10 are critically involved in the pathogenesis and progression of OC. A biomarker panel combining these three claudins demonstrates superior diagnostic and prognostic performance compared to individual markers and established clinical biomarkers such as CA125 and HE4. Notably, functional evidence indicates that CLDN6 plays a pivotal role in regulating malignant phenotypes, highlighting its potential as a novel therapeutic target. These findings collectively support the clinical utility of the CLDN6/9/10 axis as both a non-invasive biomarker signature and a promising avenue for targeted intervention in ovarian cancer.

Our study presented the de novo design of a two-step drug delivery system targeting Claudin-6 with enhanced anti-tumor efficacy and improved biosafety. These findings highlighted the potential of this approach to enhance the efficacy of tumor-targeting therapies and reduce adverse effects, paving the way for more effective cancer treatments.

This study represents the most extensive molecular characterization of RMC to date, identifying TROP2 and other potential therapeutic targets. Sacituzumab govitecan demonstrates potential clinical benefit, warranting further evaluation in prospective trials to confirm its efficacy and explore additional targets identified herein.

Enfortumab vedotin is an NECTIN4-targeting antibody-drug conjugate that is approved for the treatment of urothelial cancer, whereas other ADCs or derivatives that target NECTIN4, such as bulumtatug fuvedotin, SHR-A2102 and zelenectide pevedotin, are being studied in randomized phase III clinical trials. In contrast, arcotatug tavatecan, garetatug rezetecan, sonesitatug vedotin and tecotabart vedotin are anti-CLDN18.2 ADCs in phase III clinical trials for the treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinomas, and raludotatug deruxtecan is an anti-CDH6 ADC in a phase II/III clinical trial for the treatment of platinum-resistant ovarian cancer. ADCs that target cell-cell adhesion molecules are a rapidly emerging class of cancer therapeutics, and bispecific ADCs and longitudinal companion diagnostics are emerging to further improve the clinical benefits of conventional ADCs.

These results support CLDN6 as an oncofetal cell-surface antigen that may be suitable for CAR T-cell targeting in pediatric solid tumors, including those of the CNS.

We found that CLDN6 promoted chemoresistance by inducing protective autophagy in response to adriamycin (ADM) and paclitaxel (PTX). Notably, we discovered that chemotherapy increased CLDN6 expression through the reactive oxygen species (ROS)/GATA4 axis. Our results suggest that CLDN6 plays a pivotal role in breast cancer chemoresistance through protective autophagy, highlighting its potential as a therapeutic target to improve treatment outcomes of breast cancer patients.

P1, N=231, Active, not recruiting, Chugai Pharmaceutical | Recruiting --> Active, not recruiting

Approximately 20% of patients with metastatic disease relapse or develop resistance to cisplatin-based chemotherapy, despite its high effectiveness, underscoring the need for alternative therapies...However, implementation requires clinical validation, patient selection, and standardization. The landscape of TGCT treatment may change over the next ten years as a result of the integration of targeted therapies and molecular diagnostics, which may greatly increase survival rates while lowering long-term toxicity.

This study provides a comprehensive lncRNA-mRNA regulatory network and identifies biomarkers that could advance OSCC therapeutic strategies. The findings offer new insights into OSCC pathogenesis and potential targets for clinical application.

Collagen and silicone punctal plugs were placed and the patient was started on preservative free artificial tears, topical loteprednol 0.5 %, later replaced with topical prednisolone acetate 1 % drops, and brimonidine 0.2 % in both eyes. Ocular symptoms and exam findings waxed and waned with continued infusions of the ADC. This case reports an incidence of corneal pseudomicrocysts associated with TORL-1-23 treatment, which should be recognized as a potential adverse effect of this novel therapy.

P1, N=214, Recruiting, BioNTech Cell & Gene Therapies GmbH | N=147 --> 214 | Trial completion date: Jan 2040 --> Jan 2041 | Trial primary completion date: Jan 2027 --> Jan 2028