Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer (2024)

Claudin 18.2 (CLDN18.2) is a tight-junction protein. CLDN18.2-targeting strategy has cut a striking figure in CLDN18.2 positive patients with advanced gastric cancer. Zolbetuximab, the CLDN18.2 antibody, obtained a better clinical benefit in patients compared with the controlled. In phase II trials, combination treatment of epirubicin, oxaliplatin and capecitabine (EOX) + zolbetuximab achieved the optimal effects of overall survival which extended to 13.2 months with tolerable safety events, indicating its greater potential playing the second promising target in gastric cancer. This review will reveal the definitive clinical benefit CLDN18.2-targeting therapies have achieved and update the highlighting development (like chimeric antigen receptor T-cell immunotherapy) to CLDN18.2 positive patients. We then focus on 10 questions arisen from recent progress and anticipate to provide a future perspective for novel cancer treatment.

Keywords:

Claudin 18.2;
gastric cancer;
zolbetuximab;
chimeric antigen receptor therapy

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Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer (2024)

FAQs

What is Claudin 18.2 in gastric cancer? ›

Claudin-18.2 (CLDN18. 2) is a member of the tight junction protein family and is a highly selective biomarker with frequent abnormal expression during the occurrence and development of various primary malignant tumors, including gastric cancer (GC) and esophago-gastric junction adenocarcinomas (EGJA).

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Which of the following is the most successful treatment for gastric cancer? ›

Surgery is the most common part of stomach cancer treatment plans, and most patients will have surgery at some point. There are several different surgical procedures called gastrectomies that involve removing a portion or all of the stomach where the cancer is present.

What is the targeted therapy given to treat gastric cancer? ›

Trastuzumab (Herceptin)

Trastuzumab has the brand name Herceptin. It's a type of targeted treatment called a monoclonal antibody. Monoclonal antibodies work by attaching to proteins on or in cancer cells. Human epidermal growth factor receptor 2 (HER2) is a protein that makes cells grow and divide.

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What is the first line treatment in advanced gastric cancer? ›

For patients diagnosed with advanced gastric or gastroesophageal cancer that is not amenable to surgical intervention, the standard of care for first-line treatment consists of fluoropyrimidine and platinum-based chemotherapy.

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What is the prognostic impact of claudin 18.2 in gastric and esophageal adenocarcinomas? ›

Claudin 18.2 expression itself has no impact on prognosis and is not related to any tumor subtype.

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What is the role of claudins in cancer metastasis? ›

Depending on where the tumor originated, claudin overexpression or underexpression has been shown to regulate cell proliferation, cell growth, metabolism, metastasis and cell stemness. Epithelial-to-mesenchymal transition is one of the most important functions of claudin proteins in disease progression.

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What is the best treatment for advanced stomach cancer? ›

If surgery isn't an option, systemic chemotherapy might be recommended instead. It might be used if the cancer is too advanced or if you're not healthy enough to have surgery. Chemotherapy might help control cancer symptoms. HIPEC is an experimental treatment that might be an option for stage 4 stomach cancer.

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What is the prognosis of advanced gastric cancer? ›

The overall 5-year survival rate for these patients ranges from almost zero for patients with disseminated disease to nearly 50% for patients with distal, resectable regional disease. Even apparent localized disease only shows a 5-year survival rate in patients with proximal gastric cancer of only 10% to 15%.

What is the most aggressive stomach cancer? ›

Diffuse type is an aggressive form of cancer in which cells (that never come together to form tumors) scattered throughout the stomach grow and spread rapidly. This form is more commonly found in the upper portions of the stomach or involves the entire stomach.

What is the success rate of targeted therapy? ›

While chemotherapy offers around a 30% success rate, targeted therapy is successful in up to 80% of cases.

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Can targeted therapy shrink cancer? ›

Some targeted therapies called angiogenesis inhibitors interfere with these signals to prevent a blood supply from forming. Without a blood supply, tumors stay small. Or, if a tumor already has a blood supply, these treatments can cause blood vessels to die, which causes the tumor to shrink.

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What is the newest treatment for stomach cancer? ›

The Food and Drug Administration (FDA) has amended its 2021 accelerated approval of the immunotherapy drug pembrolizumab (Keytruda) as part of treatment for some people with advanced stomach cancer and gastroesophageal junction (GEJ) cancer.

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What is the second-line systemic therapy in advanced gastric cancer? ›

In a phase II study, patients with recurrent or metastatic gastric cancer who received second-line therapy consisting of olaparib and pacl*taxel achieved increased survival when compared to patients receiving pacl*taxel alone (13.1 vs. 8.3 months, HR=0.56; p=0.010), without a difference in median PFS (52).

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What is Stage 4 advanced gastric cancer? ›

Stage IV (also called stage 4) stomach cancer

In stage IV, cancer has spread to other parts of the body, such as the lungs, liver, distant lymph nodes, and the tissue that lines the abdomen wall. Stage IV stomach cancer is also called metastatic stomach cancer.