Cancer

Molecular vulnerabilities and biomarkers of telomere maintenance states for exploitation in cancer treatment

Therapies targeted at telomere lengthening mechanisms are expected to be a very effective and specific way of treating cancer. To provide a resource for exploiting telomere biology in cancer diagnosis and treatment, the CRU has characterised telomere maintenance mechanisms in approximately 1000 cancer-derived cell lines, representing more than 30 different types of cancers. This project, completed in collaboration with the Welcome-Sanger Institute (Cambridge UK), provides a dataset of telomere biology measures of unprecedented scale that uncovers under-appreciated complexity of telomere maintenance states in cancer. The CRU have used this dataset, in conjunction with proteomic data generated by ProCan® and other ‘omic data sets, to identify cancer cell vulnerabilities, therapeutics and biomarkers associated with telomere biology. The outcome of these studies will be applied in the development of therapeutic approaches for precision medicine cancer treatment.

Understanding the ALT mechanism in cancer 

Since the CRU discovered the ALT mechanism in 1996, it has proven far more difficult to understand than telomerase. ALT involves complex networks of genes required for DNA repair and chromosomal structure. Three key players for ALT have been identified (ATRX/DAX/His3.3), but investigations indicate that there is more to be discovered in this space. The CRU is using the C-circle assay (discovered in the CRU), proteomics and next generation genomic sequencing to further interrogate the ALT mechanism. These investigations utilise isogenic panels of cell lines the team has engineered over the past decade, while also leveraging the Group’s more recent 1000 cell line study, as well as emerging data from ongoing studies of cell lines and tumour tissue derived from ALT cancers such as osteosarcoma, Ewing sarcoma and brain cancers.

Proteomic profiling for improved health outcomes in multiple myeloma

Despite the availability of new drugs and cell therapies, multiple myeloma remains an incurable disease, with treatment failure, disease evolution and high rates of relapse being the primary causes of fatality. To improve survival of patients with multiple myeloma, more sophisticated diagnostic methods are needed to precisely classify disease subsets, predict therapy response and identify the treatment most likely to cure the disease in individual patients. Toward this goal, the CRU is working to establish methodology and reference data sets for pioneering the application of state-of-the-art protein profiling (proteomics) technology in the diagnosis and classification of multiple myeloma.