Abstract A37: Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers

Luteinizing hormone releasing hormone receptors (LHRHR) are overexpressed on cancer cell surfaces of the prostate, ovary, breast, and cervix'each of which reflect a health disparity in the African American, Latino, and Asian communities. Chemotherapy in combination with surgery, radiation, and hormone therapy is commonly used to treat these cancer types. Novel LHRH analogues have been discovered and optimized to selectively deliver cytotoxic agents to the tumor mass as a means to improve therapeutic index and efficacy while sparing normal tissues. We have synthesized several generations of 20% down-substituted One Bead One Compound (OBOC) focused libraries composed of select D- and L- amino acids, carboxylic acids, sulfonyls, and isocyanates, and screened under highly stringent conditions against LHRHR positive, negative, and overexpressing cell lines. Our novel LHRH analogues out performed clinical LHRH analogues [d-Trp6] LHRH and [d-Lys6] LHRH in binding affinity against LHRHR in vitro. Cell adhesion ligands for prostate (PC3N, PC3M), breast (MDA MB-231, MCF7), ovarian (A2780), and cervical cancer (HeLa, SiHa) have been discovered, and their use as tumor-homing agents for diagnostic and therapeutic purposes is being explored in xenograph models. Our preliminary studies utilizing our docetaxel loaded disulfide cross-linked nanoparticle platform demonstrate a therapeutic efficacy against PC3M-luc subcutaneous xenograft. We believe these drug loaded nanocarriers will be able to target and kill cancer cells more efficiently while minimizing side effects compared to current treatments when decorated with our highly specific and high affinity LHRH ligands. This approach is a promising strategy for future clinical development. Citation Format: David J. Olivos, III, Mary R. Saunders, Yuanpei Li, Nasir Al Awwad, Kit S. Lam. Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A37.