Role of Ribosomal Protein Ubiquitination in Chemotherapy- and Stress-induced RNA disruption in Tumour Cells

We have observed that chemotherapy agents can induce RNA degradation in tumour cells, a phenomenon called “RNA disruption”. Interestingly, we also found that high tumour RNA disruption after 2-3 cycles of chemotherapy predicts for complete tumour destruction after treatment and improved cancer patient survival. We and Rna Diagnostics, Inc. are using this knowledge to identify patients with non-responding tumours early in treatment, who might benefit from discontinuing chemotherapy (and its side effects) and moving on to alternate treatments.

The Tumour Cell Senescence Index: A Possible Tool to Identify Patients At High Risk of Treatment Failure During Neoadjuvant Chemotherapy

While promoting the destruction of the majority of tumour cells, chemotherapy treatment in cancer patients also permits chemo-resistant, senescent tumour cells to survive. Such senescent cells can live off dead tumour cells during and after chemotherapy. They can then form new tumours, resulting in disease progression. We have recently observed that chemotherapy treatment also induces strong degradation of an important macromolecule in tumour cells called ribosomal RNA.

Effects of Chemotherapy and Immune Cells on Ribosomal RNA Degradation (RNA disruption) in Tumour Cells

The business partner in this application (Rna Diagnostics, Inc.) has developed a diagnostic tool to determine whether the tumour(s) of a cancer patient undergoing chemotherapy before surgery is responding (dying) in response to treatment. This tool, called the Rna Disruption Assay (RDA), can help tailor chemotherapy, such that chemotherapy treatment is discontinued (along with its negative side effects) in patients with non-responding tumours. These patients can then move more quickly to other potentially more beneficial treatment.

A new paradigm for the discovery of anti-cancer drugs based on tumour RNA disruption

While chemotherapy drugs are effective in combating tumour growth in cancer patients, many such drugs permit the development of drug-resistant tumours and progression of the disease. We have observed that several chemotherapy agents induce the degradation of tumour cell ribonucleic acid (RNA) in the laboratory and in cancer patients. We have further shown that this RNA degradation is associated with complete tumour destruction after-treatment.

Statistical analysis of RNA electropherograms to understand the degree and nature of RNA disruption induced by anti-cancer drugs

In this project a molecular diagnostic test, named RNA Disruption Assay (RDA) will be developed. RDA measures an individual patient’s tumor response to chemotherapy and accurately predicts whether the drug regimen will lead to the elimination of the disease after the completion of the treatment. RDA is a measure of RNA structural integrity and is derived from RNA electropherograms.