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New research from Department of Physiology, Anatomy and Genetics (DPAG) has identified a new gene that allows cancer cells to survive in the typically acidic microenvironment of a malignant tumour. Researchers have discovered drugs that inhibit the gene in other medical conditions also selectively kill cancer cells at acidic pH, without damaging healthy tissue. This defines a novel strategy for targeting acidic tumour regions.

Acidic regions of a cancer tumour labelled red © Dr Jana Koth, MRC Weatherall Institute for Molecular Medicine
Acidic regions of a cancer tumour labelled red

Cancer cells create uniquely acidic environments for tumours to invade formerly healthy tissues and metastasise. Their higher metabolic rates produce greater volumes of lactic acid and CO2, and a lack of blood vessels prevent efficient wash-out of acidic waste products from the tumour. A great deal of research over the years has attempted to explain how cancer cells adapt to survive in these acidic conditions. However, presently none of the major approved therapies for managing tumour growth actively target acid handling.

New research led by Dr Johanna Michl and Professor Pawel Swietach (Department of Physiology, Anatomy and Genetics, DPAG) performed a genome-wide CRISPR-Cas9 screen to simultaneously study all genes potentially involved in cancer cell survival under acid stress. They have identified, for the first time, that a fundamental mitochondrial process called oxidative phosphorylation (OXPHOS) is the principal and most critical survival pathway in acidic tumour environments. Corresponding author Dr Johanna Michl said: “Targeting mitochondrial pathways such as OXPHOS has previously been considered a promising avenue for cancer therapy. However, we are the first to show that the efficacy of targeting mitochondrial metabolism in tumours depends on an acidic environment.”

Read the full story on the DPAG website

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