First Project: NEW DRUG for metastatic Colorectal Cancer

Since cancer is the second cause of death worldwide, there is an urgent need for more effective and personalized treatments of tumors. Metastasis development and chemoresistance to first line standard of care are the main cause of patient death in most tumor types. In colorectal cancer (CRC), the 5-year relative survival rate for patients with distant metastases is only of 15 %. Thus, there is an urgent need to develop less toxic and more effective agents for the metastatic stage of the disease.

Fortunately, current surgery-based approaches and conventional chemotherapy can be enhanced using nanomedicine.

NNL-121 targets CXCR4 receptor, a cell receptor overexpressed in 50% of metastatic colorectal cancer patients. High CXCR4 expression in tumoral tissue is associated with metastatic dissemination and indicates poor patient prognosis. This condition is shared among many other cancer types. (1,2) NNL-121 is a self-assembling protein nanoparticle conjugated to an anti-tumor drug able to selectively kill tumor cells expressing the receptor. A size in the nano range allows good biodistribution after systemic administration avoiding renal filtration. This high circulation combined with and specific targeting favors an accumulation in the tumor tissue. Preclinical results look very promising: in vivo results show that our nanoconjugated drug accumulates in primary tumor and metastatic foci with negligible presence in liver, kidney, brain or other organs. The result is a significant decrease of the number of metastatic load and primary tumor growth with very low toxicity on healthy cells.

Technology supporting the project:

Céspedes MV , Unzueta U, Aviñó A, Gallardo A, Álamo P, Sala R, Sánchez-Chardi A, Casanova I, Mangues M, Lopez-Pousa A, Eritja R, Villaverde A, Vázquez E, Mangues R. Selective depletion of metastatic stem cells as therapy for human colorectal cancer. EMBO Molecular Medicine 2018 vol: 10 (10).