Advani Lab - Dept. of Radiation Med at UC San Diego School of Medicine

Sunil Advani Lab

A long-time focus of the Advani Lab has been on the understanding and overcoming of tumor radio-resistance. An R01 funded tenured faculty, Dr. Advani and his colleagues have focused on cell signaling pathways involving the PAK-RAF signaling axis. They recently demonstrated that non-canonical, kinase independent functions of RAF mediates cell cycle progression and radio-resistance through phosphorylation of CRAF at serine 338 by PAK. In parallel, the lab is developing tumor-targeted delivery approaches to ultra-potent tumoricidal drugs that have the dual advantage of also radio-sensitizing.

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DR. ADVANI’S RESEARCH IS SUPPORTED IN PART BY A 7-YEAR, $2.5M R-37 FROM THE NATIONAL INSTITUTES OF HEALTH

Featured Articles

Selective Radiosensitization

This study reports that potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize tumors based on surface receptor expression. These findings establish an alternative therapeutic paradigm for ErbB-based Radiosensitization using antibodies to restrict radiosensitizers delivery.

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CRAF-driving Tumor Radioresistance

This study reports that treatment of tumors with ionizing radiation drives p21=activated kinase 1 (PAK1)-mediated phosphorylation of CRAF on pS338 triggering a kinase-independent mechanism of DNA repair and therapeutic resistance. This work establishes a role for CRAF in the DNA damage response independent of its canonical function as a kinase.

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Novel Radiosensitization Approach

This study describes the ability of the anti-tubulin agent monomethyl auristatin E (MMAE) to function as a potent radiosensitizer and to selectively be delivered to tumors using an activatable cell-penetrating peptide targeting matrix metalloproteinases and RGD-binding integrins (ACPP-cRGD-MMAE).

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