Team

Inhibition of RAS-related Pathways in Malignant Peripheral Nerve Sheath Tumors (MPNST)

Malignant peripheral nerve sheath tumors (MPNST) present a major clinical challenge due to complex cytogenetic aberrations and high metastatic potential, coupled with a lack of effective treatments. Dr. Lev’s research centers on the hyperactive Ras signaling pathway, which is a key driver of MPNST growth resulting from the loss of the tumor suppressor protein neurofibromin.

To systematically identify vulnerabilities in these tumor cells, Dr. Lev and her research team are leading a comprehensive effort to evaluate targeted single-agent and multi-agent interventions. Because cancer progression involves complex, redundant signaling networks, her work explores whether simultaneously targeting multiple Ras-related kinases provides superior cytotoxic effects compared to single-agent approaches.

Key Aims & Focus Areas

• Establish an MPNST Tissue Bioresource: Building a robust clinical database and creating a clinically annotated MPNST tissue microarray at UT MD Anderson Cancer Center to support ongoing research and discovery.
• Identify Key Dysregulated Ras Kinases: Utilizing RNA interference (siRNA knockdown) in MPNST and Schwann cell lines to pin down specific Ras-related kinases essential for tumor cell proliferation and survival.
• Evaluate Combination & Targeted Therapies: Testing traditional drugs, novel investigational compounds, and biological inhibitors alone and in combination to systematically target downstream Ras signaling and overcome therapy resistance.

Through these efforts, Dr. Lev’s project aims to delineate crucial signaling nodes in MPNST, establishing a rational foundation for translating effective targeted kinase therapies into clinical treatment strategies for patients.

Dr. Lev subsequently joined the faculty at MD Anderson Cancer Center as an Associate Professor in the Department of Cancer Biology and served as Principal Investigator of the MD Anderson Sarcoma Research Laboratory. During her seven-year tenure, her laboratory made pioneering contributions to the understanding of the molecular genetics of soft tissue sarcomas and desmoid tumors, identifying genetic mutations, mechanisms of chemoresistance, and therapeutic targets within dysregulated signaling pathways, including the Ras pathway in Malignant Peripheral Nerve Sheath Tumors (MPNST). Her work helped advance the development of targeted therapies for aggressive connective tissue cancers.

In 2013, Dr. Lev returned to Israel to resume the practice of cancer surgery, specializing in breast cancer. She was appointed Professor of Surgery at Tel Aviv University, becoming the first female surgeon in Israel’s history to attain the rank of full Professor of Surgery. Throughout her career, Dr. Lev has published extensively in the fields of sarcoma biology and translational cancer research and is internationally recognized for her contributions to connective tissue tumor oncology. She continued her impactful work as a surgeon, researcher, and mentor until her passing in 2020.