Deciphering Heterogeneity to provide treatment for metastatic Endometrial cancers

Endometrial cancer (EC) is the most common pelvic gynecological malignancy in industrialized countries. Although most women are cured of their disease, approximately 20% either present with metastatic disease or develop metastases after initial therapy. In these cases, the cancer is universally fatal. Understanding the metastatic process can contribute to diagnostics that better determine which cancers will metastasize, and the development of therapies that specifically exploit vulnerabilities in metastases. Unfortunately, the processes that enable ECs to metastasize are poorly understood. No specific recurrent genetic events that drive the metastatic process has been identified. Such genetic events may be challenging to identify, as only small fractions of cells in the primary tumor harbor such alterations. Studies describing in detail the complexity of heterogeneity within clones of primary endometrial tumors and how this affect treatment responses as well as ability to metastasize are lacking. This project will combine genomic analyses, including technologies to track cells, with unique cancer models for clonality to pinpoint targets in tumor cell clones of endometrial cancer. Our ambition is to identify new strategies for better treatment of metastatic endometrial cancer.

Endometrial cancer (EC) is the most common pelvic gynecological malignancy in industrialized countries. Although most women are cured of their disease, approximately 20% either present with metastatic disease or develop metastases after initial therapy. In these cases, the cancer is universally fatal. Understanding the metastatic process can contribute to diagnostics that better determine which cancers will metastasize, and development of therapies that specifically exploit vulnerabilities in metastases. Unfortunately, the processes that enable ECs to metastasize are poorly understood. It has been shown that the metastatic process requires phenotypes that are not necessary for primary tumor formation, such that only a subset of cells in the primary tumor could gain these phenotypes. However, no specific recurrent genetic events that drive the metastatic process has been identified. Such genetic events may be challenging to identify, as only small fractions of cells in the primary tumor harbor such alterations. Although clonal heterogeneity and tumor evolution is well known, and their importance for cancer progression and for the clinical outcome of cancer treatments is widely appreciated, studies describing in detail the complexity of this heterogeneity within clones of primary endometrial tumors and how this affect treatment responses as well as ability to metastasize are lacking. This project will combine genomic analyses, including technologies to track cells, with unique cancer models for clonality to pinpoint targets in tumor cell clones of endometrial cancer. Our ambition is to identify new strategies for better treatment of metastatic endometrial cancer.