Two research projects funded by the National Cancer Institute

  • Research
Published on November 9, 2023 Updated on November 9, 2023

on the October 26, 2023


Two research projects led by teams from Université Côte d'Azur were successful in the National Cancer Institute’s 2023 PLBIO (Free research in Biology and Cancer Sciences) call for projects. This call finances projects involved in the fight against cancer, with the aim of acquiring new knowledge of tumor pathologies, developing new tools and opening new therapeutic perspectives.

The project “Autophagy in bone tissue: Impact on tumor development & therapeutic interest”

This project, awarded 556,000 euros for the period 2024-2027, is coordinated by Dr. Valérie Pierrefite-Carle, (TIRO-MATOs, UMR E4320 Université Côte d'Azur, CEA) in partnership with the University of Nantes (Dr. Dominique Heymann, Centre de Cancérologie de l'Ouest).

Bone is a complex microenvironment and an attractive site for tumor colonization, both for metastases and for primary tumors such as osteosarcoma. Autophagy is a major process that degrades and recycles damaged macromolecules and organelles. This project aims to understand how the modulation of autophagy in the bone microenvironment can affect tumor development.

The specific objectives of this project are:

- to identify changes in the bone matrix induced by defective autophagy in osteoblasts, the cells in charge of producing this matrix;
- to analyze the development of breast and prostate cancer bone metastases in an autophagy-deficient or autophagy-competent bone microenvironment;
- to analyze autophagy in samples from patients with bone tumors;
- to generate an autophagy inducer with bone tropism and analyze its effect on the development of bone tumors using an interdisciplinary approach.

This work could ultimately make it possible to reduce/delay the onset of bone metastases, thus increasing the survival rate of patients.

The project “Characterization and targeting of mRNA translational repression in non-small cell lung cancer”

This project, funded in the amount of 742,000 euros for the period 2024-2028, is coordinated by Dr. Patrick Brest, (Institute for Research on Cancer and Aging, Nice (IRCAN) INSERM U1081, CNRS UMR 7284, Université Côte d’Azur, IHU RespirERA) in partnership with the team of Dr. Chloé Féral (IRCAN, Université Côte d’Azur) and Dr. Arnaud Hubstenberger (Valrose Institute of Biology (IBV), Université Côte d’Azur, CNRS, Inserm), Prof. Paul Hofman (CHU-Nice), Dr. Emmanuel Chamorey (Centre Antoine Lacassagne, Nice), and Prof. Raymond Mattingly (East Carolina University, USA).

Despite the emergence of promising new therapies, lung adenocarcinoma remains the deadliest cancer in the world. Eligibility for targeted therapies is based primarily on DNA markers whereas most treatments target proteins, indicating a mismatch between the available markers and the choice of drug targets. The proven low correlation between mRNA and protein levels, due to the presence of untranslated and stored mRNA, demonstrates the need for a better understanding of the mechanisms of translation regulation to treat patients effectively. The researchers aim:
1.    to identify biomarkers associated with translation regulation in stress resistance and tumor invasion in order to identify patients with poor prognoses;
2.    to analyze how post-transcriptional regulation is involved in this progression, and to develop genetic and pharmacological approaches to target p-body remodeling in tumors.
Ultimately, the results are intended to initiate a paradigm shift by focusing on translational regulation as the cornerstone of cancer resistance and aggressiveness.