eP278 - Resistance to FOLFOXIRI in Colorectal Cancer Mediated by a Reversible Metabolism Reprogramming

Sunday, June 2, 2024

11:27 AM – 11:32 AM ET, USA

Location: Baltimore Convention Center, Room 318-320

ePoster Presenter(s)

Shuohui Dong, MD (he/him/his)

Assistant research fellow
Qilu Hospital of Shandong University
Qilu Hospital of Shandong University
Jinan, Shandong, China (People's Republic)

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.

Author(s)

ZC

Zhiqiang Cheng, n/a

associate professor
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
Jinan, Shandong, China (People's Republic)

Disclosure information not submitted.
Xiang Zhang

Surgeon
Qilu Hospital of Shandong University
Qilu Hospital of Shandong University
Jinan, Shandong, China (People's Republic)

All of the relevant financial relationships listed below have been mitigated.
This individual has no financial relationships with ineligible companies.
ZL

Zitian Liu, n/a

107 of Wenhuaxi road
Qilu hospital of Shandong University
Jinan, Shandong, China (People's Republic)

Disclosure information not submitted.
GY

Guangwei Yang, n/a

107 of wenhuaxi road
Qilu hospital of Shandong university
JINAN, Shandong, China (People's Republic)

Disclosure information not submitted.
xZ

xiang Zhao, n/a

Doctoral Candidate
Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Jinan, Shandong, China (People's Republic)

Disclosure information not submitted.
KW

Kexin Wang, n/a

Chief of the Department of Colorectal Surgery
Qilu Hospital of Shandong University
Jinan, Shandong, China (People's Republic)

Disclosure information not submitted.
SH

Sanyuan Hu, n/a

professor
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
Jinan, Shandong, China (People's Republic)

Disclosure information not submitted.

Purpose/Background: The eradication of neoadjuvant chemotherapy-resistant colorectal cancer (CRC) represents a significant clinical challenge that has yet to be addressed.Methods/Interventions: This study aimed to investigate the underlying mechanisms of chemoresistance in FOLFOXIRI neoadjuvant chemotherapy by utilizing patient-derived xenograft (PDX) and PDX-derived organoid (PDXO) models of CRC patients.Results/Outcomes: The utilization of whole exome sequencing (WES) in the analysis of PDX tumors revealed that the residual tumors that persisted following treatment with FOLFOXIRI maintained their genetic characteristics, while exhibiting distinct transcriptomes, metabolomics, and histologic features compared to untreated tumors. Upon cessation of treatment, these residual tumors gave rise to chemosensitive tumors that displayed similar transcriptomes, metabolomics, and histological features to those observed in untreated tumors. Collectively, these findings provide evidence that cancer cells have the ability to enter a reversible drug-tolerant persister (DTP) state as a means to evade chemotherapy-induced cell death. Furthermore, our study revealed that DTPs undergo a reversible metabolic reprogramming triggered by mitochondrial functions.Conclusion/

Discussion: This study offers valuable insights into the utilization of metabolic reprogramming by cancer cells to promote the DTP state, thereby identifying potential therapeutic avenues for targeting DTPs.