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SDH defective cancers: molecular mechanisms and treatment strategies

Jiaer Wang1,2, Tao Yuan1, Bo Yang1,3

  • 1Engineering Research Center of Innovative Anticancer Drugs, Ministry of Education, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Hangzhou, China.

Cell Biology and Toxicology
|April 26, 2025
PubMed

Insights

Succinate dehydrogenase (SDH) deficiency in cancer disrupts energy production and promotes tumor growth through succinate accumulation. Understanding these mechanisms aids in developing targeted cancer therapies.

Area of Science:

  • Biochemistry
  • Oncology
  • Cell Physiology

Background:

  • Succinate dehydrogenase (SDH) links the TCA cycle and electron transport chain, crucial for ATP production.
  • SDH deficiency is observed in various cancers, leading to decreased activity and succinate buildup.
  • Accumulated succinate acts as an oncometabolite, driving tumor progression.

Purpose of the Study:

  • To review SDH deficiency types and pathological features in tumors.
  • To discuss SDH's role in carcinogenesis, categorizing mechanisms as succinate-dependent or independent.
  • To summarize current and preclinical management strategies for SDH-deficient tumors.

Main Methods:

  • Literature review of SDH deficiency in cancer.
  • Analysis of SDH's role in tumor progression.
  • Summary of clinical and preclinical therapeutic strategies.

Main Results:

  • SDH deficiency manifests in diverse tumor types with specific pathological characteristics.
  • Defective SDH promotes carcinogenesis via succinate-dependent and independent pathways.
  • Succinate accumulation is a hallmark of SDH-deficient cancers like GISTs and pheochromocytomas.

Conclusions:

  • SDH deficiency is a key driver in specific cancers, involving succinate accumulation.
  • Targeting SDH or succinate pathways offers potential therapeutic avenues.
  • Further research into SDH-deficient tumor management is warranted for improved cancer therapeutics.
Keywords:
MechanismMedical managementSDH-deficient cancerSuccinate

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