Decoding the landscape of cancer vulnerabilities in high-risk cervical carcinomas to detect new treatment strategies
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Despite implementation of effective screening programs and vaccines, cervical cancer still has one of the highest cancer mortality rates, with over quarter of a million deaths worldwide. In 2017, we showed that cervical cancer patients with neuroendocrine (NET), undifferentiated and adenosquamous histology have significantly worse prognosis. In lack of targeted treatment, these patients receive radiation and/or chemotherapy and, unfortunately, response rates are low. In this project we aim to identify new treatments and biomarkers and thereby contribute to improving treatment of these women.
In the first part of this project, we will cultivate cells from cancers of individual patients. With the help of new cell technologies, individual genes can be silenced in large cell screens. Cell clones which do not survive, represent genes that may be essential for cancer development. By drug screens, we will test several treatments against these so-called cancer dependency genes. In the second part of the project, we will test the specific responses of selected treatments in extensive preclinical studies including cell lines and mouse models.
In the third part of the project, we will perform a large-scale genomic, molecular, radiomic and clinic-pathological classification of these rare tumors to reveal unknown treatment targets and biomarkers. Together with Prof. Santin at the Yale University, we have recently sequenced 65 neuroendocrine tumors (recently published in PNAS). This characterization will continue in the current project.
