Fighting Metastasis in Cancer Treatment

Newly introduced drug aims to tackle cancer by preventing metastasis, and therapy resistance, thereby curbing patient mortality.

Novel drug has been developed to combat cancer by halting epithelial-mesenchymal transition (EMT), metastasis, and resistance to anti-cancer treatments, which are the leading causes of treatment failure and mortality in cancer patients ().

In a study published in the prestigious journal Nature, researchers led by Pr Cédric Blanpain – WEL Research Institute investigator, director of the Stem Cells and Cancer Laboratory, Faculty of Medicine and professor at the Université libre de Bruxelles showed that Netrin- 1, a molecule expressed by tumor cells in different types of cancers, stimulates the Epithelial-Mesenchymal transition (EMT) in tumor cells and a drug targeting Netrin-1 blocks EMT in cancer.

Sharp Decline in Early-Stage Cancer Diagnoses in the U.S.
After the emergence of COVID-19 in the U.S. in March 2020, the number of diagnoses for all stages experienced a significant decrease.

‘Researchers have created a groundbreaking drug that addresses cancer by blocking epithelial-mesenchymal transition (EMT), metastasis, and treatment resistance, pivotal factors contributing to treatment failure and cancer-related deaths. # Cancer, #Drug, #Metastasis ’

Justine Lengrand, Ievgenia Pastushenko, Sebastiaan Vanuytven, and her colleagues found that cancer cells presenting EMT express high levels of Netrin-1 and its receptor UNC5B. Researchers have shown that increasing Netrin-1 promotes EMT while targeting Netrin-1 decreases EMT.

In collaboration with NETRIS Pharma which has developed a therapeutic antibody specifically blocking the interaction between Netrin-1 and its receptor UNC5B, the ULB researchers have shown that the administration of the therapeutic antibody leads to a reduction in tumor formation but also blocks EMT in these tumors, which reduces their ability to give rise to metastases and sensitizes the tumor cells to chemotherapy.

"We are extremely happy and excited to have identified the first drug that can target EMT in vivo and therefore reduce the formation of metastases and resistance to chemotherapy", explains Justine Lengrand, the first author of the study.

Confronting Cancer's Most Lethal Traits

After having demonstrated the effectiveness of the anti-Netrin 1 antibody in preventing EMT in animal models, the ULB researchers then collaborated with researchers from the University of Lyon and Nétris Pharma to study the effect of this drug on EMT in patients with endometrial cancers.

How Outdoor Air Pollution May Increase Prostate, Colorectal Cancers' Risk?
Communities with elevated average BMI levels may encounter a disproportionately higher risk of cancer due to exposure to NO2.

The researchers and clinicians administered the anti-Netrin antibody to patients in clinical trials in France. These studies showed that the administration of the therapeutic antibody was well tolerated and showed no toxicity.

More importantly, they showed on biopsies from the tumors taken before and after administration of the drug, that this therapy decreased EMT in patients with endometrial cancers.

Lung Cancer Patients' Survival May Affect by Wildfire Exposure
Identification of medically high-risk populations, such as lung cancer patients is important for natural disaster preparedness and response efforts.

“This is a major world premiere, we have discovered a new drug that can reduce EMT, decrease metastasis and stimulate the response to chemotherapy in preclinical models. In a second study, the researchers and clinicians provided the proof of principle for the medical application of our fundamental discovery and showed that the administration of the anti-Netrin-1 antibody inhibits EMT in cancer patients. We have now to assess whether the administration of the anti-Netrin-1 antibody and the reduction of the EMT will provide to the cancer patients a better clinical response to chemotherapy and immunotherapy” comments Professor Cédric Blanpain, the leader of this project.

The Belgo-French collaboration identifies novel innovative therapeutic combinations to sensitize tumors to chemotherapy and prevent tumor progression, the development of metastases, and resistance to anti-cancer therapy.

“In the long term, it will be necessary to determine the effectiveness of this new therapy on the survival of patients with endometrial cancers and assess the efficacy of this new drug combination for the treatment of other types of cancers presenting EMT such as lung or breast cancers” comments Professor Cédric Blanpain, the last author of the study.

Reference:

Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer - (https://www.nature.com/articles/s41586-023-06367-z)

Source-Eurekalert