Neuropilin-2 Inhibitor as a Potent Therapy for Prostate Cancer Bone Metastasis
Abstract
There is no effective therapy to-date that can effectively cure prostate cancer bone metastasis. Systemic chemotherapy can be used to treat metastatic prostate cancer, however, the tumors often will become resistant. Our studies suggested that a cell-surface protein called neuropilin-2 is highly expressed in metastatic prostate cancer cells especially when they are in bone and is responsible for their ability to resist therapy. Based on our preliminary results, we hypothesized in the current proposal that a neuropilin-2 targeting drug in combination with chemotherapy should be an effective treatment strategy for prostate cancer patients with bone metastasis. Recently, with the help of computer modeling-based screening strategy and supportive wet laboratory-based studies, we have identified a FDA approved drug, which can specifically block neuropilin-2. In this proposal, we will test the potential of this drug in the combination with chemotherapy in preclinical mouse model of prostate cancer bone metastasis. We will also study a blood-based biomarker, which will can indicate high neuropilin-2 expression in metastatic bone tissues. This marker will thus help to stratify metastatic patients, who will be best suited for neuropilin-2 targeting drug therapy. Successful completion of the proposed project will eventually lead to the anti-neuropilin-2 drug as a front-line therapy for the lethal metastatic prostate cancer. Since this anti-NRP2 drug is an FDA approved drug for other disease-specific uses, the detailed information about it regarding its pharmacology, formulation and potential toxicity to human is known. Re-purposing this drug to treat lethal prostate cancer can be done with ease. We expect within 5-8 year time period from now, the drug can complete the necessary clinical trials and can be integrated as a therapy for prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1190758
Entities
People
- Benjamin A Teply
- Kaustubh Datta
Organizations
- University of Nebraska Medical Center