With the second grant to therapy

(Press-News.org) Tumor cells carry specific genetic mutations that actively drive the growth and spread of cancer. When mutations in particular genes are present, standard treatments such as chemotherapy or radiation often become significantly less effective, requiring more targeted therapeutic approaches instead. One of these genes is called KEAP1.

Mutations in the E3-ligase KEAP1 are the focus of a new research project at Julius-Maximilians-Universität of Würzburg (JMU). José Pedro Friedmann Angeli, Professor of Translational Cell Biology at the Rudolf Virchow Center – Center for Integrative and Translational Bioimaging, is responsible for the project. He has secured a proof-of-concept grant worth 150,000 euros from the European Research Council (ERC) for this project.

Attacking a metabolic weak point

“With the support of the proof-of-concept grant, we plan to develop a new therapy for the treatment of KEAP1-mutated lung cancer,” says Friedmann Angeli, describing the aim of the project. Together with his team, he is focusing on a recently identified transporter that is involved in the sulfite secretion of tumor cells where his group has identified a first of its kind inhibitor to be used to block this transporter. As a result, toxic sulfite accumulates in the tumor cells, especially in KEAP1-mutated cancer cells, thereby initiating their death.

“We believe that the grant funds will enable us to further develop our lead compound SulfExstatin-1 and convert this metabolic vulnerability into a potential targeted therapy,” says Friedmann Angeli. He hopes that this further development could then represent “a much-needed treatment option for this aggressive type of cancer with a poor prognosis.”

Proof of Concept Grant

Only scientists who have an ongoing ERC grant and now wish to exploit a research result from their project on a pre-commercial basis are eligible to apply for a Proof of Concept Grant.

The aim of a Proof of Concept project is to test the market potential of such an idea. The ERC thus funds measures for further development with a view to the application readiness, commercialization, or marketing of the idea.

Specialist in a specific form of cell death

At the end of 2023, Friedmann Angeli received a two-million-euro ERC Consolidator Grant, which was used to carry out the preliminary work. There, together with his team, he identified the transporter whose inhibition is now intended to initiate the death of cancer cells.

The award winner is a pioneer in the field of ferroptosis. This special form of cell death is triggered by the accumulation of oxidized lipids and is associated with many pathological conditions, including cancer and neurodegeneration. At the same time, inducing ferroptosis in many difficult-to-treat tumors can be an effective strategy to eliminate them.

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