Nav: Home

Acidic pH: The weakness of cancer cells

July 31, 2018

Cancer cells are known to acidify their environment and, consequently, the interior of the cells themselves is alkalised. In principle, this deregulation should hinder the development and proliferation of these cells. However, exactly the opposite happens in cancer. A computational study co-authored by computational chemist Miquel Duran-Frigola, from the Institute for Research in Biomedicine (IRB Barcelona), has demonstrated that cancer cells proliferate less and in a less robust manner when their internal pH is lowered, that is to say it becomes more acidic. This finding thus reveals opportunities for new therapeutic approaches to tackle the disease.

Using hundreds of thousands of data from previous biochemical assays and a database on the gene expression of cancer cells, the researchers have developed a computational model that analyses how variations in pH affect the activity of almost 2000 metabolic enzymes. "We are a computational lab and we are devoted to systems biology. We wanted to address the question on a large scale," says Miquel Duran-Frigola, Associate Researcher with the Structural Bioinformatics and Network Biology lab, headed by ICREA researcher Patrick Aloy. "Understanding the link between metabolic pathways that work better under different pHs can give us an idea about the mechanisms used by cancer to survive at basic pH," explains Duran-Frigola.

Acidification as an objective

The researchers have confirmed the hypothesis that they initially formulated. According to this hypothesis, if cancer cells proliferate easily in an alkaline environment, then they would be more vulnerable under acidic conditions. This paves the way to considering the acidification of the cancer cells themselves, combined with more conventional therapies, as a good therapeutic strategy.

New therapeutic targets

Furthermore, the researchers have identified the metabolic enzymes that work synergistically with intracellular acidity in the development of cancer, thus revealing these molecules as possible therapeutic targets. Indeed, five of these potential targets have already been tested in the lab using breast cancer cell lines and have yielded promising results.

"This work is still very academic, but we believe that some of the targets identified are ready to be tested in animals, thus allowing us to move into more advanced pre-clinical trial stages," says Miquel Duran-Frigola. The study, which has been performed in collaboration with the Moffitt Cancer Center and the University of Maryland, both in the US, has been published in Nature Communications.
-end-
The study has been done in collaboration with the University of Maryland and the MOFFIT.

Reference article:

Erez Persi, Miquel Duran-Frigola, Mehdi Damaghi, William R. Roush, Patrick Aloy, John L. Cleveland, Robert J. Gillies & Eytan Ruppin

Systems analysis of intracellular pH vulnerabilities for cancer therapy

Nature Communications (2018): DOI 10.1038/s41467-018-05261-x

Institute for Research in Biomedicine (IRB Barcelona)

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".