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Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
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Neural signaling modulates metabolism of gastric cancer

Hanne-Line Rabben1,2, Gøran Troseth Andersen1, Magnus Kringstad Olsen1

  • 1Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.

Iscience
|February 18, 2021
PubMed

Insights

Targeting nerve-cancer metabolism reverses gastric cancer progression. This study identifies key metabolic targets and demonstrates a novel therapeutic strategy combining vagotomy with specific inhibitors, showing promise for patient treatment.

Area of Science:

  • Oncology
  • Metabolic Research
  • Cancer Biology

Background:

  • Tumors are complex ecosystems involving cancer cells and the tumor microenvironment (TME).
  • Gastric cancer exhibits specific metabolic reprogramming, crucial for its growth and survival.

Purpose of the Study:

  • To identify the metabolic signature of gastric cancer.
  • To investigate the effect of vagotomy on metabolic reprogramming in gastric cancer.
  • To propose and validate a novel therapeutic strategy targeting nerve-cancer metabolism.

Main Methods:

  • Metabolic profiling of human and mouse gastric cancer models.
  • Vagotomy intervention in mouse models to assess metabolic changes.
  • Identification and validation of drug targets including SNAP25, mTOR, PDP1/α-KGDH, and glutaminolysis.
  • Therapeutic efficacy assessment using intratumoral BoNT-A with systemic RAD001 and CPI-613 in mice.

Main Results:

  • Vagotomy reversed metabolic reprogramming in gastric cancer, shifting from glutaminolysis to OXPHOS/glycolysis.
  • Normalization of energy metabolism in cancer cells and the TME was observed post-vagotomy.
  • Combined therapy (BoNT-A, RAD001, CPI-613) significantly improved overall survival in mice.
  • The proposed therapeutic strategy demonstrated feasibility in patients.

Conclusions:

  • Neural signaling plays a critical role in modulating tumor metabolism in gastric cancer.
  • Targeting nerve-cancer metabolism represents a promising therapeutic avenue.
  • This study provides a rationale for the clinical translation of this novel strategy for gastric cancer treatment.
Keywords:
CancerCancer Systems Biology

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