A humanized monoclonal anti-claudin1 antibody (anti-cldn1 mab) for treatment of hepatocellular carcinoma (hcc)
Hepatocellular carcinoma is the most frequent primary liver cancer and owing to its very aggressive nature is amongst the leading cause of cancer mortality worldwide (IARC). The number of liver cancer-related deaths in Europe in 2018 amounted to 77 375, and this number is expected to keep rising, reaching an estimated number of more than 100 000 deaths in 2040 (IARC). Major causes include the hepatitis B and C viruses, alcoholism, Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. All of these medical conditions trigger liver fibrosis by damaging the liver and are closely associated with the development of HCC. As a matter of fact, more than 80% of HCC develop in fibrotic or cirrhotic livers. Early stages of liver cancer do not usually produce symptoms, and many challenges are associated with the screening of HCC, leading to its late diagnosis. The absence of effective drug treatment for HCC makes its resection the first curative option with most of the patients experiencing HCC recurrence within 5 years. All these factors contribute to the poor prognosis of the HCC patients. Sorafenib is the only currently approved systemic therapy for advanced HCC in the EU, only prolonging survival by an average of 3 months, the treatment often leads to drug resistance. Indeed, intra-tumor heterogeneity strongly constrains the therapeutic benefit of precision medicine and triggers drug-resistant sub-population of cells. Consequently, persistent treatment of drug-resistant tumor cells may accelerate tumor progression, suggesting that inappropriate and continual use of a compound on drug-resistant cancer cells is not recommended. Thus, there is an urgent unmet medical need to identify and to validate the therapeutic efficacy of new valuable molecules – i.e. targeting the existing drug-resistant cell populations -that could be used in monotherapy or in combination therapy with FDA-approved drugs to improve HCC treatment responses.