ONCOTHERANOSTICS · Advanced Theranostic Nanomedicines for Oncology. Development of new combinatorial therapies for primary and metastatic Breast Cancer.

Advanced Theranostic Nanomedicines for Oncology. Development of new combinatorial therapies for primary and metastatic Breast Cancer.

Despite dedicating enormous research and socioeconomic efforts, cancer remains as the second cause of death globally. Furthermore, the economic impact of cancer is significant and it is increasing. Among different tumor types, breast cancer has the highest incidence among women, causing 684996 deaths worldwide in 2020, and being the fourth cause of cancer related deaths. Brain cancer has a very poor prognosis and the treatment options very limited. Thus, any improvement in cancer treatment will have a great impact in the health of millions of patients and will benefit the society as a whole. In recent years, cancer immunotherapies have gained significant importance. These therapies are designed to activate the immune system against cancer cells. The field has been recently revitalized with the discovery of immune checkpoints such as programmed cell death protein-1 (PD-1) and its ligand (PD-L1). As the regulators of the immune system activation, these immune checkpoints are utilized by cancer cells to escape immune surveillance. Immunotherapies aim to trigger an immune response against cancer cells by blocking immune checkpoints used by cancer cells to escape immune destruction. PD-L1 is often overexpressed in cancer and it has been successfully exploited for immune therapy in different tumor types, such as melanoma, non-small cell lung carcinoma and renal cell carcinoma. However, treatment outcomes have not been as effective in other cancers such as breast cancer or gliomas. The explanation for this lack of efficacy is multifactorial, but several studies point towards cancer aberrant metabolism as one of the key causes. Although most cancers exhibit an aberrant metabolism, one common feature shared by most of them is the increased levels of phosphocholine (PC) and total choline-containing compounds. These changes have been attributed to the overexpression and increased activity of choline kinase (Chk)-α in malignant cells. The main objective of ONCOTHERANOSTICS is to assess the mechanism of immunotherapies failure and to develop novel approaches that allow to overcome tumor resistance. This overall objective is divided in multiple specific objectives, one of them being completed during this period and the second still under study. The first specific objective is to investigate the molecular links between tumor metabolism, cancer acquired immune resistance and immunotherapies failure in vivo in a breast cancer model. The second specific objective is to assess the link between PD-L1 and tumor metabolomics in gliomas.

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