Background

Cancer continues to exert a heavy toll after cardiovascular diseases (CVD), accounting for nearly 10 million deaths worldwide in 2020, and nearly one in six deaths. Europe accounts for 22.8% of the total cancer cases and 19.6% of the cancer deaths, although it represents 9.7% of the global population. Lung cancer (LC) is the leading cause of cancer mortality in the world. Over the last 2 decades, sex-based LC incidence disparities have increased, with higher incidence in females, despite lower tobacco use among them. Three years relative survival rates after the diagnosis of LC have improved from 9% in the 1990s up to 18% (peaking to 30% in PDL-1high LC) in 2021 with the advent of targeted and immunotherapies, but remain poor. Hence, prevention and early detection of LC became a worldwide priority. Two major randomized clinical trials conducted by investigators of this consortium showed that low dose computed tomography (LDCT) based- LC screening can significantly reduce LC mortality by 8-26% for men and 26-61% in women. Results from the National Lung Screening trial (NLST) indicated that the risk for LC incidence and mortality was 3-4 times higher for those with a positive versus negative baseline screen. Similarly, the NELSON trial concluded that the 5.5-year risk for screen-detected LC was 1.0% and 48.3% for those with a negative and positive baseline screening, respectively. While 70% of all clinical cases are detected at an advanced stage, about 55% of all cases in the LDCT arm of NLST and NELSON were detected in stages I or II. Risk assessment to advise LDCT LC screening program represents an unmet medical need.

Goals

Goals

  1. Validate in both retrospective biobanks and large prospective cohorts, classifiers representing four functional drivers of chronic inflammation detecting CVD individuals pre-symptomatic and at early stages of lung carcinogenesis: this will allow to implement patient stratification for preventive interventions based on dysmetabolism, innate immunosuppression, clonal hematopoiesis or gut microbiota dysbiosis (4 main drivers).
  2. Demonstrate the actionability of such biomarkers: develop and test specific interceptive measures for each of the 4 main drivers of inflammation using food supplements or pharmacological agents (on the top of diet and lifestyle modifications) to return to homeostasis

The progress

Achieved Milestones

January

2023

Study Launch

Study Launch
Pre-clinical Testing
Data Analysis
Wrap up
Current status

Zitvogel Lab

Laurence Zitvogel

Principal Investigator

Marine Fidelle

Fellow

Carolina Alves Costa Silva

Fellow