Decoding the Heterogeneity and Regulation of Cancer Metabolism.

A defining hallmark of cancer is an altered metabolism which is critical to support a rapid proliferation. However, the cancer metabolism also differs not only from individual to individual, but also from tumor to tumor. Hence, targeting metabolism has the potential to improve precision medicine.

In fact, inter-tumor heterogeneity represents a major reason for unsuccessful treatment of Lung Adenocarcinoma, the most common form of lung cancer in Sweden.

Treatment based on genetics has proven to be unsuccessful for many patients, suggesting that there are other factors involved.

We have identified four new molecular regulators that control glucose metabolism by stabilizing metabolic enzymes, on the protein level.

Importantly, they are strongly associated with poor prognosis, found to be highly expressed in lung cancer patients compared to normal counterparts – allowing a therapeutic window.

With this project, that will run for 4-years, we will delineate the mechanism(s) how they regulate metabolism by implementing comprehensive state-of-the-art technologies coupled to gain- and loss-of-function approaches in vitro and in vivo. We will reveal their diagnostic and prognostic value as well as test their direct targetability.

This proposal has a strong translational focus, and we expect to reveal new knowledge underlying the clinical heterogeneity that could pave the way for novel tailored therapeutic and diagnostic strategies to improve precision oncology.