No Back-up Plan: Loss of Isozyme Diversity as a Promising Therapeutic Strategy for Cancer
Abisola Z Kehinde1, Seth J Parker1,2
1Department of Biochemistry & Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract:
Metabolic rewiring in cancer cells supports many aspects of tumor growth. Understanding the mechanisms that result in metabolic rewiring, such as altered enzyme expression, is key to identifying therapeutic vulnerabilities that selectively target cancer cells. In this issue of Cancer Research, Marczyk and colleagues analyze matched tumor-normal enzyme expression across 14 different cancer types and report that cancer cells exhibit a general loss of isozyme diversity (LID) relative to corresponding normal tissue. The authors hypothesized that the presence of a cancer dominant isozyme may reduce metabolic plasticity and uniquely sensitize cancer cells to isozyme-specific inhibitors. Several LID targets were identified, including acetyl-CoA carboxylase 1 (ACC1), which the authors validated using a clinically available inhibitor of ACC1/2. This study is the first to systematically evaluate isozymes affected by LID, which represents a promising strategy to target the unique metabolic demands of cancer. See related article by Marczyk et al., p. 1698.
Insights
Cancer cells show reduced isozyme diversity, a finding that may offer new therapeutic targets. This loss of diversity could make cancer cells vulnerable to specific enzyme inhibitors, presenting a novel strategy for cancer treatment.
Area of Science:
- Biochemistry
- Oncology
- Metabolomics
Background:
- Metabolic rewiring is crucial for tumor growth and survival.
- Altered enzyme expression is a key mechanism driving cancer metabolism.
- Targeting cancer-specific metabolic vulnerabilities is a promising therapeutic strategy.
Discussion:
- Cancer cells exhibit a significant loss of isozyme diversity (LID) compared to normal tissues across various cancer types.
- This LID may reduce metabolic plasticity, potentially sensitizing cancer cells to targeted inhibitors.
- The study systematically identifies and evaluates isozymes affected by LID.
Key Insights:
- A general loss of isozyme diversity (LID) is observed in cancer cells versus normal tissue.
- A dominant isozyme in cancer might limit metabolic adaptability, creating a vulnerability.
- Acetyl-CoA carboxylase 1 (ACC1) is identified as a potential LID target, validated with a clinical inhibitor.
Outlook:
- LID represents a novel and promising strategy for developing targeted cancer therapies.
- Further research into LID mechanisms could uncover more selective vulnerabilities.
- Targeting LID may lead to more effective and less toxic cancer treatments.
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