Philippe Roux and his team seek to understand the molecular mechanisms by which oncogenes transform a normal cell into a cancerous one. This knowledge is crucial for the discovery of novel therapeutic targets and to decipher the molecular causes of resistance to treatment.

Research theme

Cell signaling mechanisms enable cells to integrate environmental signals and generate appropriate responses. Their dysregulation, particularly through mutations in signaling proteins, contributes to numerous diseases. Cancer is the most striking example, often resulting from the activation of proto-oncogenes (KRAS, BRAF, PIK3CA) or the inactivation of tumor suppressor genes (PTEN, APC, TP53). The main objective of the Roux laboratory is to decode these signaling networks in cancer cells in order to promote the development of new therapeutic strategies.

Research objectives

1. Functional decoding of the RAS/MAPK pathway in melanoma

The RAS/MAPK pathway, which is hyperactivated in more than 85% of melanomas, is a major driver of transformation, cellular plasticity, and therapeutic resistance. The Roux laboratory uses an integrated platform combining advanced phosphoproteomics, BioID/TurboID proximity approaches, and computational analysis of signaling networks to 1) map the proximal and distal effectors of the pathway, 2) discover previously unexplored molecular relays, and 3) define how these signaling nodes orchestrate proliferation, invasion, plasticity, and the emergence of resistance to therapies.

This work has led to the identification of new effectors of the RAS/MAPK pathway, whose functional characterization is progressing rapidly, paving the way for their evaluation as next-generation therapeutic targets.

2. Detection of oncogenic vulnerabilities using proteogenomics and CRISPR screening

Using a collection of isogenic cell models expressing major human oncogenes (KRAS, PIK3CA, MYC, HER2), the Roux laboratory is using an integrated approach combining transcriptomics, quantitative proteomics, phosphoproteomics, and high-throughput CRISPR/Cas9 screening to 1) identify genetic and metabolic dependencies specific to each oncogene, 2) characterize the adaptive networks and compensatory mechanisms that allow tumor cells to escape pharmacological inhibition, and 3) reveal rational therapeutic combinations capable of preventing, circumventing, or reversing resistance.

These systematic multi-omic analyses highlight previously unsuspected vulnerabilities, providing a powerful framework for prioritizing targets and designing innovative therapeutic strategies for aggressive cancers.

3. Discovery of new immunotherapeutic targets in adult and pediatric leukemias

The Roux laboratory has adapted and optimized cell surface chemoproteomics approaches to directly interrogate primary samples of acute myeloid leukemia (AML). By combining selective chemical labeling, affinity purification, and high-resolution mass spectrometry, the team 1) compiles a comprehensive and quantitative inventory of surface antigens expressed by leukemia cells, 2) identifies rare tumor markers that are enriched in molecular subgroups or associated with disease progression, and 3) distinguishes targets with a particularly favorable tumor-normal ratio for therapeutic development.