RAS Oncogenic Signaling and Therapeutic Resistance

Research Description

Cancer remains one of the leading causes of death worldwide, and despite remarkable therapeutic advances, many patients with solid tumors still face limited treatment options and poor long-term outcomes.
One of the major challenges in oncology is the capacity of tumor cells to escape therapy through dynamic adaptation and molecular rewiring, ultimately undermining even highly targeted treatments.
Addressing this challenge requires a deep mechanistic understanding of how cancers arise, evolve, and resist.
The Ambrogio Lab investigates RAS oncogenes as central drivers of cancer, with a focus on understanding how aberrant molecular signaling initiates tumorigenesis and shapes response to targeted therapy. RAS-driven tumors represent a major clinical challenge due to the limited durability of current treatments, which are frequently compromised by the rapid emergence of drug resistance. Our research also aims to uncover the early mechanisms of transformation that enable tumor cells to expand and eventually to adapt and survive therapeutic pressure.
By integrating advanced in vivo lung cancer models with functional genomics, we dissect how oncogenic signaling networks are rewired during disease progression and treatment.
This allows us to identify critical vulnerabilities that can be exploited to improve therapeutic outcomes.
Ultimately, we seek to bridge fundamental cancer biology with translational application by defining predictive biomarkers and rational treatment strategies. Our goal is to develop a mechanistic framework that informs how to prevent or overcome resistance, advancing more effective and durable therapies for patients with RAS-driven cancers.

Funding

• 2025-2026: ERC Proof of Concept (POC) Grant.
• 2024-2027: WWCR (WorldWide Cander Research)
• 2023-2028: MIUR FARE (Italian Ministry of University and Research)
• 2022-2027: AIRC (Italian Association for Cancer Research)
• 2021-2027: ERC Consolidator Grant
• 2021-2022: ILCF Young Investigator Award
• 2020-2023: Harvard-Armenise Career Development Grant