Research Project
9339437
The overall objective of this proposal is to develop an in vitro process by which cancer stem cells (CSC) can be isolated from primary human tumor biopsies or tissues, expanded without losing critical elements of stem cell qualities, and then used for preclinical and clinical applications. During this fast track proposal, KIYATEC will employ an integrated, functional and unbiased scientific strategy, in order to establish and standardize processes which are able to isolate and expand cancer stem cell populations derived from immortalized and patient?derived xenograft cell lines and primary human tissues. Due to a combination of scientific and commercial factors, but driven by the large unmet clinical need in small cell lung cancer (SCLC), KIYATEC will focus on developing its CSC cultivation technology and methods on SCLC, a relatively rare and uniformly fatal cancer affecting men and women of all ethnicities. Debulking and curative surgeries that permit extra tissue for research are rarely performed, which has limited available tissue for cell lines and patient derived xenografts. There is, however, strong evidence that a tumor initiating or cancer stem cell populations exist in SCLC, both in primary tumors and in circulating tumor cells obtained from patient whole blood[1]. The ability to isolate and expand the rare CSC population from limited biopsy samples from patients and or the CTC population from ?liquid biopsies? of patients would greatly aid the academic research community as well as biopharmaceutical companies who are increasingly focusing on rare tumor types with high unmet clinical need. By the end of phase I performance, KIYATEC will have identified the processes required to isolate and expand to greater than 10^7 functional and undifferentiated SCLC CSC from existing SCLC patient derived xenograft cell lines. By the end of phase II, KIYATEC will have confirmed the ?stemness? of the expanded CSC derived from primary SCLC patient tissues, while developing and molecularly and functionally characterizing a SCLC PDX ?bank? from at least 10 different SCLC patients. Importantly, this project is perfectly aligned with KIYATEC?s mission to provide direct and positive impact on patients with cancer, through accelerating the drug development of targeted therapeutics which will have the potential to eliminate the CSC population, the ultimate driver of metastasis, resistance, relapse and death due to cancer.
