Which mechanism is behind the efficacy and specificity of your anti-cancer drug candidate?

Mitochondria play a pivotal role in cancer cell survival, through the coordination and control of vital cell parameters such as energy production and apoptosis. This organelle is therefore a promising target for the development of anti-cancer drugs and bio-therapies.

Our MitoPathway® platform offers assays characterising cancer or immune cells and cellular responses to drugs.

Mitochondria are a valuable target in oncology for four reasons. First, to cope with a hostile context, cancer cells tend to reprogramme their metabolic pathway to provide energy flexibility and ensure cell survival, leading to the “Warburg effect” whereby tumours favour the glycolytic pathway for energy production. Second, specific cancer types – such as leukaemia, melanoma, pancreatic cancers – can rely on OxPHOS activity as part of primary or acquired resistance to chemotherapy. Third, cancer cell resistance to therapies is also associated with altered regulation of apoptosis, with cells protecting themselves from mitochondrial outer membrane permeabilisation (MOMP) by playing on levels of Bcl-2 family proteins. Fourth, mitochondrial plasticity provides an advantage to cancer cells and contributes to tumour resistance to drug; with adapted mitochondria numbers, structure and function.

Immunotherapy has demonstrated great power and holds promise for future cancer treatment strategies. The metabolism of immune cells is a key component of their proliferation, activation, differentiation, and response to tumours. Depending on their differentiation and memory status, T cells – naïve, memory, killer, Treg, CAR-T… – use distinct metabolic pathways and display a specific OxPHOS/glycolysis balance. Maintaining OxPHOS activity is determinant to preventing T cell exhaustion and ensuring sustainable immune responses and/or memory. Metabolic reprogramming is a new approach, aiming to improve the ability of T cells to withstand metabolic stress and the tumour microenvironment. It should ultimately lead to more effective and adaptive T cell therapies – involving TIL and CAR-T cells – and consequently increased patient survival.

Assays on our MitoPathway® platform can help identify pro-apoptotic drugs. They are also useful for the development of immunotherapies as they provide strong indications of metabolic fitness and cell-fate for potential T cell therapies.

MitoXpert® can be used to assess mitochondrial function in tumour cells or isolated tumour mitochondria. Our assays cover the evaluation of: