Exploiting microfluidic technology to predict chemoradiation responses in HNSCC

Project Description

Head and neck cancer (HNC) is the 6th most prevalent cancer worldwide. The mainstay of treatment involves a combination of radiation and cisplatin. Despite improvements in the delivery of these treatments, and enhanced guided radiotherapy, 3yr survival rates remain below 60%. This is largely due to locoregional recurrence and metastasis to the cervical lymph nodes, indicating resistance to the treatments leading to salvage surgery. Therefore a more selective evidence based treatment on a personalized level from the outset is required. The HNC research group in Hull have developed bespoke microfluidic devices, which are able to maintain pieces of a patients’ tumour tissue whilst being subjected to different combinations of drugs and irradiation. This approach allows the response of the tissue to be analysed, either by studying the release of soluble factors and measuring changes over time, or by analysing the tissue itself and identifying the most effective regimen on an individual patient basis. The authors believe that a sample of the patient’s own tissue is the closest representation of the whole 3D tumour available ex vivo and will mimic how the patient’s tumour will respond.
The principle aim of the project, is to correlate the response seen in the laboratory with that seen in the patient, so providing evidence that the data obtained using the microfluidic devices is directly applicable in the clinical setting. A cohort of 20 HNSCC patients, recruited over a 10 month time frame, will have samples taken at the time of diagnostic biopsy and the tumour tissue maintained on the microfluidic device will have the same treatment applied to it as is experienced by the patient, e.g. chemoradiotherapy. Alternative treatments, based on those clinically available, will be applied to additional biopsies (or resection specimens where possible) to determine whether improved options could have been available to the patient and to investigate heterogeneity. The tissue will be maintained on the device for a minimum of 4 days during which time secretions from the tissue will be monitored for markers of cell death. At the end of the experiment, the tissue will be removed from the device and analysed in terms of morphological changes, alterations in cell death and proliferation markers using immunohistochemistry and Western blotting. The patients will be followed up over 2 years by the clinical team and monitored for response to treatment; the clinical outcomes will be correlated with the responses seen in the laboratory. If, as we believe from extensive preliminary work, the correlation of clinical response with the device is high, it is envisaged that the methodology could be simply translated into the clinic, facilitating the development of translational alogarithms, based on evidence obtained on a personalised level.