Development of Targeted Chemotherapy for the Treatment of Metastatic Prostate Cancer
Abstract
Prostate cancer remains one of the deadliest cancers. Advanced and metastatic prostate cancer is initially controlled with androgen deprivation therapy. Unfortunately, most cases eventually progress into metastatic castration-resistant prostate cancer and become refractory to this treatment. Current chemotherapies for metastatic castration-resistant prostate cancer provide no cure or are aimed at palliations of symptoms. Suboptimal efficacy of currently used therapeutics is in part related to their limited tumor-specificity and insufficient levels of delivery. Given intravenously, most of the therapeutics are diluted over the entire body and only small amounts reach diseased tissue with even less able to penetrate solid tumors where they can be most effective. This leads not only to poor treatment outcome, but also severe side effects. Therefore, there is an urgent critical need for development of more effective prostate cancer therapies with improved therapeutic effectiveness and safety profile to patients. Our previous research has identified an active cellular transport pathway that can pump antibodies armed with therapeutic cargo directly into solid tumors and metastatic lesions. We have identified a specific disease biomarker that is concentrated in the tumor vasculature and unique to this cellular pump and have subsequently developed the humanized recombinant antibody specific to this biomarker that is capable of penetrating deeply and specifically inside prostate tumor tissue as the result of pumping. Here, we propose to use this highly specific and unique antibody for precision delivery of select, very potent chemotherapeutics directly into prostate tumors and metastatic lesions. Depending on the particular therapeutic cargo and linker chemistry evaluated in the study, we expect to identify those therapeutic reagents that are most effective in treatment of metastatic prostate cancer. Extending our previous work, we will evaluate the potential of this strategy for targeted chemotherapy of prostate cancer in several preclinical models of metastatic prostate cancer, including tumors that are castration-resistant or unresponsive to conventional chemotherapy treatment. If successful, this novel targeting strategy could significantly enhance therapeutic efficacy and reduce undesirable side effects in patients suffering from prostate cancer. The preclinical research proposed here will establish a path for the development and potential clinical translation of this type of novel biotherapeutics for treatment of metastatic prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310148
Entities
People
- Adrian Chrastina
Organizations
- Proteogenomics Research Institute for Systems Medicine
- United States Army