Microfluidic Inflammatory Tumor Model for Drug Discovery in Patients with Systemic Infection
DescriptionIn cancer patients, systemic bacterial infections are serious complications during chemotherapy, affecting patients' prognosis and survival. Clinical studies have demonstrated a correlation between bacterial infection and tumour progression. However, due to the inherent heterogeneity and complexity of bacterial infections, both cancer-promoting and anticancer effects have been reported in the presence of bacteria-mediated inflammation. A well-defined model is needed to perform quantitative and dynamic analyses of bacteria–tumour interactions to accurately assesstumour response under bacteria-mediated inflammation. Due to its rapid processing rate, small size and multiplex assay capabilities applicable even to patient blood samples, microfluidics technology is important for advancing point-of-care testing. In vitro drug screening platforms can be beneficial for personalized medicine because they integrate the micro-environmental cues that mimic the tumour microenvironment. In previous studies, we demonstrated the use of integrated microfluidic platforms to establish patient-derived tumour models and develop downstream drug screening applications. However, it is extremely technically challenging to evaluate the effects of tumour-related microbiomes on drug efficacy, which limits the efficacy of conventional treatment methods in the presence of systemic infections. Therefore, it is necessary to develop new combinatorial treatments that use antibacterial agents to improve prognoses and outcomes. In the proposed project, we will develop a microfluidic inflammatory tumour model by combining the advantages of microfluidics and integrated in vitro systems to realise point-of-care drug testing and discovery. The parameters of the inflammatory tumour model will be defined by considering the types of bacteria and the sites of infection. The dimensions of the microstructures should be relevant to the micrometastasis formed in vivo. Moreover, the conditions optimal for tumour growth will be incorporated alongside the integrated components previously optimised using our patient-derived models. Systematic studies will be conducted to obtain quantitative outputs that provide insights into how bacterial distribution in tumour tissues affects cancer cell phenotypes and tumour progression. Although cellular drug concentrations in vivo are influenced by clinical pharmacokinetics, in vitro tools remain pivotal for predicting tumour response to new combinatorial treatments that focus on toxicity or synergy by assessing the half-maximal inhibitory concentration (IC50). The microfluidic bacteria–tumour platform will be automated through computer-controlled programming to realise the continuous monitoring of tumour dynamics under the influence of bacterial infection. In sum, the proposed novel microfluidic inflammatory tumour model will provide a unique means to evaluate the combination of anticancer and antimicrobial drugs, thereby advancing automated medical technology for point-of-care testing.
|Effective start/end date||1/01/22 → …|