A project led by the researcher Laia Josa-Culleré receives 1.5 million of euros to study the elimination of cancer stem cells

The project SeleCStem, coordinated by the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), belonging to the Spanish National Research Council (CSIC), has obtained an ERC Starting Grant of 1.5 million of euros from the European Research Council to study the elimination of cancer stem cells. These cells, which have characteristics of normal stem cells such as regeneration and differentiation, represent a very small number within the tumour, and are not affected by treatments such as chemotherapy. After treatment, these cells can regenerate the tumor, often being responsible for relapse, and even producing metastasis.

SeleCStem, led by the researcher Laia Josa-Culleré, will study how to eliminate these cells by developing innovative drugs that leverage the expression of the enzyme aldehyde dehydrogenase (ALDH) in cancer stem cells, achieving a much more selective treatment than other therapies under development.

“The ALDH enzyme is overexpressed in cancer stem cells, something that we will take advantage of to develop drugs and achieve their elimination with three different approaches”, explains Laia Josa-Culleré, researcher at IQAC-CSIC and principal investigator of the project.

This research will be carried out in 5 years and will develop three complementary methods to eliminate the cells. In the first, the research team will use the activity of the ALDH enzyme, which oxidises aldehydes to acids, to accumulate drugs within cancer stem cells.

The second method of study is the release of the drug inside the cell. The drug will be administered in an inactive form, and the action of the ALDH enzyme will cause the release of the active compound.

Finally, the team will develop drugs that inhibit the ALDH enzyme (and consequently eliminate tumour stem cells) by shining light on them, but not in the dark. In the future, the tumour will be illuminated to achieve a localised effect and to avoid effects on other tissues, since healthy stem cells also overexpress ALDH.

At the end of the project, some of these methods will be combined to achieve even higher levels of selectivity.

“Getting this grant represents a turning point in my career. I will focus my research on developing innovative chemical strategies to fight cancer stem cells. The ERC-Starting Grant allows me to form the top-level team that begins this work. I couldn’t be happier!” says Josa-Culleré.

The project, which will count on scollaborators specialised in the ALDH enzyme and in the study of tumour stem cells, will begin with breast cancer cells for the proof of concept, and the most advanced molecules will also be studied in colon cancer and glioblastoma.