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Related Experiment Video

Updated: Sep 11, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
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Identification of Anticancer Target Combinations to Treat Pancreatic Cancer and Its Associated Cachexia Using

Feng-Sheng Wang1,2, Ching-Kai Wu1, Kuang-Tse Huang1,2

  • 1Department of Chemical Engineering, National Chung Cheng University, Chiayi 621301, Taiwan.

Molecules (Basel, Switzerland)
|August 14, 2025
PubMed
Summary

This study identifies novel therapeutic targets for pancreatic cancer and its associated cachexia using systems biology. Combinatorial targeting shows robust effects, offering new avenues for treatment.

Keywords:
biomarker identificationcancer metabolismconstraint-based modelingdrug target discoveryfuzzy optimizationnested hybrid differential evolution

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Area of Science:

  • Systems biology
  • Metabolic modeling
  • Oncology

Background:

  • Pancreatic cancer often involves cancer-associated cachexia, leading to muscle wasting and metabolic dysfunction.
  • Existing treatments may not address both cancer progression and cachexia simultaneously.

Purpose of the Study:

  • To develop a systems biology framework for identifying simultaneous therapeutic targets for pancreatic ductal adenocarcinoma (PDAC) and its associated cachexia (PDAC-CX).
  • To leverage cell-specific genome-scale metabolic models (GSMMs) for target discovery.

Main Methods:

  • Extended the human metabolic network (Recon3D) with protein synthesis, degradation, and recycling pathways.
  • Reconstructed cell-specific GSMMs for PDAC, PDAC-CX, and healthy counterparts using transcriptomic data.
  • Employed Parsimonious Metabolite Flow Variability Analysis and fuzzy multi-objective optimization for target identification.

Main Results:

  • Identified medium-independent metabolic biomarkers.
  • Eight combinatorial targets demonstrated robust, medium-independent effects in both PDAC and PDAC-CX cells.
  • Key targets include knockout of SLC29A2, SGMS1, CRLS1, RNF20-RNF40 complex, and upregulation of CERK, PIKFYVE.

Conclusions:

  • The integrative strategy provides novel therapeutic avenues for both pancreatic cancer and cachexia.
  • This approach aims for improved specificity and reduced off-target effects in translational oncology.