Specific Targeting and Delivery of Therapeutics to Cancer Cells Based on the Tumor Microenvironment

Tuesday, April 5, 2016
1:00 pm, MRB 200 Conference Room

Dr. Damien Thévenin

Department of Chemistry, Lehigh University

Specific Targeting and Delivery of Therapeutics to Cancer Cells Based on the Tumor Microenvironment

A plethora of cancer targeting therapies aimed at improving effectiveness and diminishing off-target cytotoxic effects have been developed and hold the promise of being curative options for defined subsets of cancers. However, preclinical and clinical evidence demonstrates that therapy strategies based on the targeting of specific proteins is significantly hampered by tumor heterogeneity, which can promote tumor evolution, and lead to loss of cell surface proteins, and eventually, to therapy resistance and disease progression. Moreover, while over-expression provides a window of selective targeting, targeted uptake into normal tissues is seen, and has the potential to lead to unacceptable toxicity profiles. Thus, alternatives are desperately needed to circumvent these limitations.

Our approach is based on the pH(Low) Insertion Peptide (pHLIP), a unique delivery peptide that can selectively target tumors in mice based solely on their acidity rather than a specific marker. My group focuses on developing new strategies to inhibit cancer cell and tumor growth by delivering therapeutics to cells using pHLIP. I will present our recent progress in (1) inhibiting cancer cell proliferation and tumor targeting through the delivery of monomethyl auristatin derivatives, (2) modulating the activity of G-Protein coupled receptors by interfering with their cytoplasmic domains, and (3) promoting apoptosis in cancer cells by inducing mitochondrial membrane disruption using antimicrobial peptides.