Preclinical Modelling and Therapeutic Development for Other Cancer Indications

Abstract public domain (NIH RePORTER)

The following collaborative projects co-led by CCR Investigators are presently in different stage of completion at CAPR: 1. A collaborative work with Dr. Michele Yohe's lab, on tolerance and efficacy assessment of dual BRD4/PI3K inhibitors with or without Histone Deacetylase (HDAC) inhibitors in PDX models established from clinically very challenging RAS-driven pediatric solid tumors known to be refractory to multiple drug treatment strategies. 2. CAPR has completed a significant project in collaboration with CCR investigators Dr. Carol Thiele and Dr. Jack Shern to test a BET domain inhibitor alone or in combination with a topoisomerase I inhibitor in Patient Derived Xenografts (PDX) of pediatric rhabdomyosarcoma and neuroblastoma. 3. CAPR is advancing its early-stage partnership efforts with Dr. Laurie Krug's laboratory on establishing and characterizing a unique collection of PDX models for chemotherapy naive vs. chemotherapy-experienced Kaposi's sarcoma (KS) tumors induced as a result of lost immunologic surveillance for KS virus in HIV-infected patients. Once successful, CAPR will employ these preclinical resources towards therapeutic assessment of various treatment options in these KS-PDX models, such as doxil, ademaciclib, and pacritinib therapeutics to measure and compare responses to these drugs in naive and recurrent KS cases. 4. In collaboration with CCR investigator Dr. Jaydira del Rivero and NIDDK researcher Dr. Sunita Agarwal, scientists in CAPR pancreatic cancer modelling program commenced importation, retooling and adoption for preclinical assessment purposes a model for multiple endocrine neoplasia malignancy type driven by tissue-specific loss of MEN1 gene. The initial objective of this study is to assemble a MEN1-driven model in which the functions of MEN1 will be specifically abolished in pancreatic beta-cells what has been previously shown to lead to insulinoma malignancy in these animals. CAPR plans to explore this model in a large-scale preventive study using a well-known diabetes formulation metformin as a promising chemo-preventive agent considered for future transition to assessment in clinical trials. This study is currently ongoing.