Claudin 18.2 and its role in advanced gastric cancers

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August 2022: The most apical portion of polarised epithelial and endothelial cells contains tight junctions, which are specialised membrane domains. The transmembrane proteins known as claudins, which are essential parts of tight junctions and have extracellular loops, are prospective targets for both diagnostic and therapeutic approaches. They might be crucial in the development of tumours and inflammation. In several epithelial malignancies, changes in claudin expression have been demonstrated to promote tumour growth, affect signalling cascades, and impair tight junction function. Tight junctions are damaged in malignancies, and claudin proteins lose their main function. Many malignancies, such as gastric cancer (GC), hepatocellular carcinoma (HCC), biliary tract cancer (BTC), breast cancer, renal cell carcinoma, pancreatic cancer (PC), non-small cell lung cancer (NSCLC), and mesothelioma, have improperly regulated claudins.

GC and PC are two malignancies that frequently express claudin 18.2, a member of the claudin family. Except for the gastric mucosa, healthy tissues do not express claudin 18.2. A highly effective chimeric IgG1 mAb that binds to claudin 18.2 on the surface of tumour cells, zolbetuximab, was recently created and is being tested in clinical studies. Notably, zolbetuximab plus standard chemotherapy as a first-line therapy increased median survival in claudin 18.2-expressing GC patients compared to chemotherapy alone in a phase II trial (NCT01630083). This encouraging finding shows that in order to expand the clinical applicability of this innovative drug to treat various cancer types, clinical trials utilising it are required. The widespread expression of claudin 18.2 is a significant and remarkable finding for the treatment of cancer given that patients who are positive for human epidermal growth factor receptor 2 (HER2) and who are currently being treated with the novel agent trastuzumab make up only 10-15% of all cases of GC (21).

The status of claudin 18.2 in various tumour types has not been thoroughly investigated using immunohistochemistry, which is significant (IHC). We carried up a prospective claudin 18.2 IHC investigation in a cohort of patients with different solid cancer tumours to look into the function of claudin 18.2 as a biomarker.

 

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Susan Hau is a distinguished researcher in the field of cancer cell therapy, with a particular focus on T cell-based approaches and cancer vaccines. Her work spans several innovative treatment modalities, including CAR T-cell therapy, TIL (Tumor-Infiltrating Lymphocyte) therapy, and NK (Natural Killer) cell therapy.

Hau's expertise lies in cancer cell biology, where she has made significant contributions to understanding the complex interactions between immune cells and tumors.

Her research aims to enhance the efficacy of immunotherapies by manipulating the tumor microenvironment and exploring novel ways to activate and direct immune responses against cancer cells.

Throughout her career, Hau has collaborated with leading professors and researchers in the field of cancer treatment, both in the United States and China.

These international experiences have broadened her perspective and contributed to her innovative approach to cancer therapy development.

Hau's work is particularly focused on addressing the challenges of treating advanced and metastatic cancers. She has been involved in clinical trials evaluating the safety and efficacy of various immunotherapy approaches, including the promising Gamma Delta T cell therapy.

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