Integrating Cancer Target Discovery with Drug Delivery Platforms: A Proof of Principle Study in Triple Negative Breast Cancer
Triple-negative breast cancer (TNBC), representing 15-20% of all breast cancers, is a devastating disease in urgent need of targeted therapeutics. No clinically effective targeted therapeutics for TNBC therapy exist to date and TNBC patients face a poor prognosis compared to that of all other breast cancer patients. To solve this challenge, we explored to combine TNBC target identification with nanoscale drug delivery systems to develop novel TNBC-targeted therapeutics. We first screened and identified intercellular adhesion molecule-1 (ICAM-1) as a novel molecular target for TNBC. Based on this new target, we rationally designed and engineered a number of ICAM-1 antibody-directed nanomedicines that selectively recognize and bind TNBC tumor in vivo, and facilitate targeted delivery of therapeutic and diagnostic agents for improving TNBC diagnosis and therapy. Our studies demonstrated an excellent potential to develop novel precision nanomedicines by integrating cancer target discovery with drug delivery platforms.
My research in the Moses Lab at Boston Children’s Hospital (BCH) is focused on developing novel targeted therapeutics for cancer therapy. A major focus is to develop novel targeted nanomedicines that inhibit cancer progression and metastasis. I have previously developed antibody-directed nanoliposomes that exhibit high tumor specificity, minimal adverse effects, and spatial and temporal delivery and release of therapeutics such as chemodrugs and siRNAs, and had been used for magnetic resonance imaging and treating of metastatic breast cancer. The central theme of this current research is to develop a novel theranostic platform that precisely ablates pancreatic tumor and the associated tumor microenvironment (stroma) using a personalized antibody-drug conjugate (ADC) combination (T/S-100), complemented by a non-invasive biomarker companion diagnostic approach to continuously monitor therapeutic efficacy and prognosis. T/S-100 is the next generation personalized ADC system developed by the Moses Lab to selectively recognize and treat different pancreatic tumors based on their tumor/stroma ratio. This unique personalized formulation of ADC will generate a cooperative synergy that is significantly more specific than conventional single-targeting therapeutics, and in turn, will improve drug delivery into pancreatic tumors. I have been working in the area of drug delivery for over a decade, where I have successfully led several multidisciplinary collaborations with other researchers and produced a number of peer-reviewed publications from these projects. These extensive experiences in drug delivery, cancer target screening/identification and animal studies have given me the necessary training for the proposed research.