In 2020, an estimated 2,68 million new cases were diagnosed and about 1.26 million people died from cancer in Europe (European Cancer Information System). Among all cancer types, 90% of cancer-related deaths, are attributed to the metastatic dissemination of the disease. A specific cellular process called EMT was shown to be necessary to allow tumor cell dissemination to secondary sites and metastatic disease. First identified as an embryonic program, EMT has been shown by many to be reactivated during tumor progression. EMT not only contributes to metastasis, but also to the regulation of tumor cell plasticity by generating stem-like cells with tumor-initiating properties and resistance to conventional therapies.
Despite significant improvements for society, in prevention, diagnosis and targeted therapies, it remains a challenge to specifically target the primary tumor mass as well as the disseminated tumor cells that present EMT features. It is now widely accepted that efficient therapies will have to target and/or block the EMT process and allow conventional therapies to efficiently kill cells to treat patients with metastatic tumors. Preliminary in vitro and in vivo results support that inhibition of our target is associated with a shift of the tumor phenotype toward a more epithelial phenotype, potentially more sensitive to regular therapy.
The aim of the NetriCan project is to validate the hypothesis that invasive tumor cells turn on the expression of our target as a survival strategy to overcome, and potentially regulate, the stressful EMT program and accomplish the metastatic dissemination cascade. Thus, using our targeted therapy will impact the metastatic disease on two battlefronts: re-epithelializing the primary tumor will increase the efficiency of conventional chemotherapy or immune-checkpoint inhibitors; and preventing the pro-survival role of our target will kill the disseminated tumor cells.
The Netrican project demonstrated for the first time a new role for our target in regulating EMT and metastases in tumors, especially for gynaecological tumors such as endometrial cancer.
