# Genomic characterization of tumor heterogeneity in recurrent small cell lung cancer through research autopsy

> **NIH NIH K08** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $248,735

## Abstract

PROJECT SUMMARY
Hui-Zi Chen, MD, PhD, is a Medical Oncology fellow in her final year of the Physician Scientist Training Program
(80% research, 20% clinic) at The Ohio State University Comprehensive Cancer Center. Dr. Chen's career goal
is to become an independent and productive physician scientist whose research will focus on identifying
mechanisms of therapeutic resistance in advanced solid tumor malignancies through combining rapid research
autopsy and genomics. As a vehicle for career development and further training towards independence, Dr.
Chen's K08 proposal focuses on the application of genomics for rapid research autopsy of patients with recurrent
small cell lung cancer (SCLC). To assist her research, she assembled a mentoring committee consisting of
Sameek Roychowdhury, MD, PhD (primary mentor, expertise in genomics and molecular diagnostics); David
Carbone, MD, PhD (co-mentor, expertise in lung cancer and therapeutics); and Lang Li, PhD (co-mentor,
expertise in bioinformatics). She has further devised a career development plan with clear objectives of (1)
gaining proficiency in leadership and project management, (2) developing expertise in the analysis and
interpretation of genomic data, and (3) obtaining continuous evaluation and feedback. These objectives will be
achieved through regular and structured meetings with mentors, formal didactics, and attendance of workshops
and regional/national conferences. Recurrent SCLC is a relentless and aggressive cancer affecting patients
globally that responds to few, if any, therapies, despite an initial response rate of 60-70% to platinum-based
chemotherapy. The study of recurrent SCLC has been limited by scarce tumor samples at time of recurrence
due to the rapid clinical demise of patients. To solve this unmet need, Dr. Chen has launched a new research
autopsy study for advanced cancer patients at OSU, one of just ten programs nationally. The main objective of
Dr. Chen's K08 proposal is to characterize genomic alterations underlying chemoresistance in SCLC. Through
a multi-disciplinary approach combining research autopsy, genomics, and bioinformatics, she will complete
whole exome sequencing (WES) of multiple metastatic tumor samples and plasma circulating tumor DNA of forty
SCLC patients with chemorefractory disease. Thus far, Dr. Chen has demonstrated the feasibility of her project
as she has already supervised the autopsy, exome sequencing and bioinformatics analysis of five patients with
recurrent SCLC. These autopsies enable the assessment of clonality in metastatic tumors and have
demonstrated that SCLC is genetically heterogeneous with early clonal diversification. Finally, Dr. Chen showed
high level of concordance between mutations in ctDNA and multiple metastatic tumors, showcasing the utility of
ctDNA in SCLC patients. Dr. Chen hopes to expand on these findings by analyzing a large cohort (n=40) of
SCLC patients. It is her long-term goal as an independent physician scientist to ide...

## Key facts

- **NIH application ID:** 10219994
- **Project number:** 5K08CA241309-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Hui-Zi Chen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $248,735
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219994

## Citation

> US National Institutes of Health, RePORTER application 10219994, Genomic characterization of tumor heterogeneity in recurrent small cell lung cancer through research autopsy (5K08CA241309-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10219994. Licensed CC0.

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