The past decade has witnessed a renewed appreciation of the complexity of cancer cell metabolism, survival and therapeutic resistance. These characteristics are especially important in the context of oral and oesophageal cancer (OOC), which is difficult to detect, is frequently diagnosed late, has few therapeutic options and has poor survival rates. Current state of the art in clinical diagnosis is limited to visual/endoscopic examination of the oral/oesophageal region and histological analysis of tumour biopsies. In addition, the predominant treatment approach is chemotherapy/radiotherapy followed by surgery. The TRACT project is focusing on developing original and innovative solutions to key challenges in OOC diagnosis and treatment through the development of methods for early and accurate diagnosis, methods for monitoring patients during therapy, approaches for prognostic stratification of patients, novel therapeutics to overcome resistance and novel target pathways, including metabolic transformation pathways.
TRACT is carrying out discovery research into biomarkers associated with OOC to develop state-of-the-art diagnostic assays for 1) earlier, more reliable detection, and 2) therapeutic response prediction. This research will improve OOC survival rates by developing biomarker-based assays for earlier, more reliable disease diagnosis and stratification of individual patients to more effective chemotherapeutic regimes. This comprehensive patient profiling provides essential information to the clinician, enabling earlier and more accurate diagnosis and the potential to administer more appropriate treatment. This approach will not only benefit the patient, with the potential for improved quality of life, disease control and minimize side-effects by administering more targeted treatment, but will also potentially lead to reduced costs for healthcare providers.
TRACT is also uncovering the molecular basis of drug resistance mechanisms in OOC and of metabolic transformation with the aim of 1) improving the efficacy of existing therapies, 2) identifying new drug targets, and 3) developing novel therapies. Initial pre-clinical testing will be carried out to support future translation to clinical studies. A greater understanding of the cellular mechanisms that contribute to chemotherapeutic resistance in OOC and that lead to metabolic transformation will enable the development of combination therapies with greater efficacy than current chemotherapeutic regimes. Targeted combination therapies hold the promise of improved response rates, decreased chemotherapeutic toxicity and enhanced survival rates.
A novel pre-clinical model of oesophageal adenocarcinoma is also being developed. These model system should better mimic the environment of the tumour within the body and tumour drug-response than traditional oesophageal cancer cell line models thus advancing the state-of-the-art.
