Investigating new treatment strategies for cervical cancer

This project aims to detect new treatment strategies for patients suffering from high-risk cervical cancer.  By genomic characterization and CRISPR-Cas12 screen, the team will detect novel cancer vulnerabilities, and by establishing 3D models from high-risk cancer patients, they will detect possible treatment strategies exploiting these vulnerabilities to treat the patients. 

Mari is allocated a four-year researcher position, and besides herself as PI, the team will also consist of a 3-year PhD position and a master student. This was the only project from the University of Bergen to be supported by the Norwegian Cancer Association for 2023.

Finding more targeted treatments for better survival and quality of life

Despite global efforts within cervical cancer screening and prophylactic vaccines, survival for patients suffering from the most severe cervical cancer subtypes is poor and treatment options few. These fast-growing and aggressive types often emerge between screening intervals and are frequently inoperable when detected. Radiochemotherapy, which confers enormous and life-lasting destruction to the pelvic tissue, is standard-of-care. With a median age of 43, even if cured, many of these women will have reduced quality of life for decades to come. Detection of targeted treatment strategies will, in addition of being curative, reduce side-effects for a range of patients and greatly improve their own and their next of kin's quality of life. Although these cancers account for only 7% of cervical cancer incidence, they are responsible for 27% of disease-specific deaths. Thus, the identification of common genomic vulnerabilities and discovery of new targeted treatments and biomarker tests for these patients is imperative to improve cervical cancer survival rates. 

Mapping the most severe cervical cancers

Mari Kyllesø Halle is eager to get all plans set in motion. "In this project, we will fine-map rare cervical cancer along with corresponding relapse biopsies by assembling all multi-omics and clinicopathological data collected at our hospital since 2001," Mari explains.

This is a highly collaborative and international project. "To increase power of detecting targetable alterations in rare subgroups, we teamed up with esteemed gynaecologist Professor Santin from Yale University, who collected and sequenced 65 neuroendocrine carcinomas, including 10 neuroendocrine carcinomas from our cohort," Mari says. "We will perform preclinical targeted drug testing towards these drivers at his lab. In parallel, we will establish an organoid library from all consenting local cervical cancer patients. By employing pre-existing facilities and infrastructure for organoid generation and CRISPR-Cas dependency assays at the Gynecological Cancer Research Group, we will perform unbiased dependency screens and design drug sensitivity panels based on identified drivers. Subsequently, we will exploit the local CC patient cohort (n=650) to identify subtype-specific clinically relevant response markers aiming for clinical implementation of our findings," she explains.

Innovation potential

This project has a strong innovation potential. "Cervical cancer dependencies will be discovered and exploited in future clinical trials," Mari says. "Utilization of comprehensive multi-omics and clinicopathological data and cervical cancer samples will reveal novel predictive and prognostic biomarkers," she concludes.

Read more here about the Cancer Association's grants (in Norwegian).