Project Details
Description
PROJECT SUMMARY
Bladder cancer is one of the top 10 most frequent cancers, yet the most underfunded cancer by NCI based on
funding dollars and ratio of funding/mortality. There has been no significant improvement in overall survival and
prognosis over the last thirty years except for the recent development of immunotherapy. After initial diagnosis
and treatment, over 60% of the BC patients will relapse within two years and progression into advanced stages
in up to 25% of patients. Therefore, almost all patients will need long-term expensive cystoscopy which makes
bladder cancer the costliest cancer (per case) of all cancer types. If a sensitive but less expensive method to
detect cancer were available, it would improve the treatment outcomes and decrease the cost. Dr. Xuefeng Liu
(PI) and his team recently invented a robust method of conditional reprogramming (CR) technology to establish
patient-derived cell models from cystoscopy or needle biopsies and urine samples of BC patients. The overall
success rate was near 100%. These urine cancer cell cultures (UCCC) provide a simple, non-invasive,
comfortable, reliable method to detect BC recurrence, and represent a living biomarker to predict patients’
response to chemotherapy and targeted therapy. Several cancer centers and laboratories including PI’s lab are
actively involved in clinical trials to validate clinical utility of the UCCC in BC clinics. Since a variety of patient-
context and collection, storage and transportation of urine samples to laboratories for cell cultures affect
enrichment and viability of cancer cells in urine samples, it is urgent needed to evaluate pre-analytical factors
of urine samples for UCCC and optimize these non-Invasive and living liquid biopsies as a routine approach in
monitoring recurrence and prediction of response of BC patients. In this application, we propose to address the
gaps by extending the work done by our team members on evaluating effects of sample processing protocols
on UCCC analysis, to further investigate effect of patient-specific context. In this application, we will first further
optimization of UCCC system to establish a culture kit for clinical applications, specifically we will optimize and
simplify conditions with co-culture kits, conditioned medium (CM), hypoxic condition for maximal efficiency and
robustness. Second, we will establish a Standard of Procedure - SOP- for urine collection and transportation in
clinics: we will test pH, temperatures, minimal cell number, a cocktail with anti-biotics and Y-27632 affect
UCCC cultures and success rate. Last, we will determine patient-context factors that affect UCCC cultures: we
will evaluate how urine timing (days before surgery, and after surgery, early morning, noon, night, drinking
water before urine collection, etc), urine volume affect cell viability and UCCC. Last, we will optimize a self-
sampling procedures for BC patients. The overall goal is to expedite UCCC clinical assay development through
evidence-based standardization of urine collection and handling practices, potentially approved by FDA as a
standard method for bladder clinics.
Status | Active |
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Effective start/end date | 09/6/23 → 08/31/24 |
Funding
- National Cancer Institute: $360,281.00
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