Abstract B66: Novel adjuvant therapy for obesity-related cancers

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 26; no. 2_Supplement; p. B66
• Main Authors: Candelaria, Pierre, Harmon, Tia, Harbuzariu, Adriana, Rampoldi, Antonio, Lipsey, Crystal, Mullen, Mckay, Kurian, Ann, Dill, Courtney, Tchio, Cynthia, Daley-Brown, Danielle, Nunez, Shakeyla, Lanier, Viola, Gonzalez-Perez, Ruben Rene
• Format: Journal Article
• Language: English
• Published: 01.02.2017
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1538-7755.DISP16-B66

Abstract Obesity incidence has reached alarming levels, particularly in minority populations: African American (AA) and Latinos. The risk of develop several cancers (i.e., breast, pancreatic and endometrial cancers) is strongly correlated to obesity. One of the essential factors involved in this relationship is leptin, the major adipokine secreted by adipose and tumor cells. Leptin is a mitogenic, proangiogenic, antiapoptotic and inflammatory factor that induces tumor growth and metastasis. Leptin has also been shown to increase cancer stem cell population and drug resistance in tumors. We have produced a potent and specific antagonist (LPrA2) that blocks leptin signaling and impairs its effects on cancer cells. LPrA2 conjugated to iron-oxide nanoparticles (IONP-LPrA2) shows enhanced bioavailability (half-life 8x higher) and inhibition effectiveness on leptin signaling in cancer cells. It is hypothesized that IONP-LPrA2 could serve as an adjuvant that increases effectiveness and allows the reduction of dosage of chemotherapeutic drugs, particularly in obesity contexts. Breast (E0771-TAM tamoxifen resistant, Py-8119, MDA-MB231, HCC1806 and MCF-7) and pancreatic cancer cells (Panc-1, BxPC-3, MiaPaca2), and their derived tumorspheres were treated with leptin, chemotherapeutics (Cisplatin, Doxorubicin, Paclitaxel and Gemcitabine) and IONP-LPrA2. Additionally, E0771-TAM and Py-8119 cells, and MDA-MB231 and Panc-1 tumorspheres were inoculated in C57BL/6J female mice (obese and lean) and female and male CD1 nu/nu mice. The mice were treated with IONP-LPrA2 during 4 weeks. Leptin induced proliferation and cell cycle progression in all cancer cells tested. Leptin also increased the number and size of breast and pancreatic cancer tumorspheres, and the levels of cancer stem cell (ALDH1, CD44, CD24, ESA), and chemoresistant (ABCB1) and pluripotent (NANOG) markers. IONP-LPrA2 treatment increased the effects of chemotherapeutics on cancer cells, and delayed tumor onset and growth. These data suggest that leptin is a mitogenic factor that increases cancer aggressiveness and survival. IONP-LPrA2 is a promising chemotherapeutic adjuvant, especially for patients suffering from obesity-related cancers. Citation Format: Pierre Candelaria, Tia Harmon, Adriana Harbuzariu, Antonio Rampoldi, Crystal Lipsey, Mckay Mullen, Ann Kurian, Courtney Dill, Cynthia Tchio, Danielle Daley-Brown, Shakeyla Nunez, Viola Lanier, Ruben Rene Gonzalez-Perez. Novel adjuvant therapy for obesity-related cancers. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B66.