Prostate cancer is the 2nd most common form of cancer among men in United States, in fact, over 26,000 men will die from PCa in the US in 2017. Researchers now believe that prostate cancer specific progression to death can be altered by a more optimal initial treatment strategy that includes systemic treatment. However, there is a paucity of material and research available to optimize the sequence or optimal combination(s) of agents and to maximize the impact of neoadjuvant treatment tailored specifically to the individual patient. This issue is heightened by the recent introduction of new drugs for androgen deprivation, chemotherapy and more recently, targeted therapy of high-risk prostate cancer (PCa). Our long-term goal is to develop an innovative treatment regimen for men with high-risk PCa to treat occult metastatic disease as well as the local tumor, by utilizing neoadjuvant therapy. The objective of this project is to assess the feasibility of implantable microdevices (IMD) to measure local intratumor response to multiple agents. The rationale of the study is that, upon successful completion of this study, we will have shown that we can obtain intratumor efficacy readouts for 19 therapies from a single patient. We will also have established whether these measurements can be used to tailor personalized and specific systemic therapy for a particular patient. With expertise in bioengineering, imaging, pathology, oncology and urology, our team is well prepared to complete this research. We will achieve our goals in the following four specific aims: 1) Develop and clinically validate a device to measure intratumor response to multiple therapies without exposing patients to systemic toxicity; and 2) Demonstrate differential local tumor response to different drugs delivered by IMD; and 3) Examine the role of biomarkers in the treatment response; and 4) To retrieve implanted IMD under MRI guidance using a retrieval device. The proposed research is significant since each tumor responds differently to different agents and lays the foundation for an IMD directed neoadjuvant trial. This will lay the ground work to prove that local intratumor response to micro doses of multiple agents can be used to effectively screen for and tailor the optimal treatment in a novel neo-adjuvant regimen. In addition, by examining the tumor for genetic and physiologic changes, we will be able to in vivo correlate potential biomarkers of tumor response to multiple drugs. Our approach is innovative as the assessment of response occurs within the patient native tumor environment - as such stroma and systemic immune response can be assessed. We will leverage expertise in a precision image guided approach to achieve precise implantation of IMDs into prostate tumors under MRI guidance, and subsequent retrieval during planned surgery.
This project will demonstrate that micro-doses of multiple agents can be used to effectively screen for and allow the specific tailoring of an optimal treatment with a neo-adjuvant regimen, for patients with high-risk prostate cancer. In addition, the research will be of significance, because we will be able to correlate potential biomarkers of tumor response to multiple drugs by examining the tumor for genetic and physiologic changes resulting from the micro-doses, thus contributing to a broader impact on onco-biology.
