MD position (w/m/d) - P13 Exploiting molecular dependencies in therapy-refractory lung cancer

Offer: MD Scholarship for doctoral thesis
Starting Date: 01.03.2025
Institute: DKTK Translational Oncology, Max-Lebsche-Platz 30 81377 München / LMU Klinikum, Marchioninistr. 15
Working Group: Interdisciplinary Research Collaboration Martin Sos (DKTK, Dept. Of Translational Oncology – Primary research site)/ Amanda Tufman (Pneumonology)

Research Topic: Exploiting molecular dependencies in therapy-refractory lung cancer

PROJECT DESCRIPTION

Lung cancer accounts for more than 40.000 cancer-related deaths in Germany alone and represents one of the deadliest cancers worldwide. A major milestone in the treatment of lung cancer patients was the discovery and therapeutic exploitation of EGFR mutations. With the help of tyrosine kinase inhibitors, the prognosis of these patients improved dramatically over the past years. However, the majority of patients treated with targeted therapies develop resistance that is thought to be linked with different types of molecularly defined adaption processes.
These resistant clones may evolve over time from cells that initially survive therapy and persist despite the lack of genetically encoded resistance mechanisms. These drug tolerant persister cells or DTPs are exquisitely sensitive to induction of ferroptosis. This opens an exciting opportunity to eliminate DTPs before they can give rise to therapy-refractory tumors. Recently, a number of new, bioavailable GPX4 inhibitors has been described and their use has the potential to revolutionize our therapeutic strategies in lung cancer patients and potentially other genetically defined tumors. However, their effects on the individual subclones of “cycling” and “non-cycling” DTPs may be different and thus the impact on growth kinetics of DTPs in animal models remains unclear. Furthermore, GPX4 inhibitor monotherapy but also combination therapy effects are likely to induce inflammatory signaling and may therefore effect the activity of individual immune cells. Overall, we propose to investigate these novel therapeutic concepts including their potential cytotoxic effects on tumor cells and the tumor microenvironment.

MANDATORY EVENTS

As holder of this scholarship you are a member of the Research Training Group (RTG) GRK 2338 “Targets in Toxicology”. The GRK represents a truly international program and benefits from an excellent scientific environment and a state-of-the-art research infrastructure.
As member of the RTG you have to participate in the lecture series “Toxicology of the lung” (once a month) and the annual Research Retreat (once a year). All other courses offered by the GRK can be attended optionally. For more information about the RTG GRK 2338 please visit the following website: https://www.grk2338.med.uni-muenchen.de/index.html

FUNDING

The scholarship will be given for 12 months, a minimum of 8 months full-time in the laboratory is required. The monthly scholarship payment is 1.037 €. In addition, a total amount of 395 € in lab consumables per month is available.

REQUIREMENTS

Medical student (LMU or TUM)

APPLICATION

If you want to apply for this scholarship, send an application (CV, project title, motivation letter and certificates) to S.Resenberger@lmu.de by 15th of January 2025. 

For project-specific questions please contact Prof. Dr. Martin Sos (martin.sos@dkfz-heidelberg.de).
Women and people from other underrepresented groups are strongly encouraged to apply and we will seek to provide any support you require to complete the project.