TRANSMIT Consortium dissected and unravelled the role of mitochondria in the metabolic reprogramming of several solid human cancers. Taking advantage of the scientific expertise of the TRANSMIT’s members and the excellent training through research and complementary skills of the 11 ESRs, the following main scientific activities were performed and related fulfilled results were achieved:
1) to educate young researchers (ESRs) in the multifaceted aspects of human cancer metabolism. In particular, ESRs showed that bioenergetic reprogramming in terms of glutaminolysis versus glycolysis and mitochondrial metabolic biomarkers strongly contribute to malignant transformation in lung and prostate cancer at least. Further, they reported the pivotal role of oxidative metabolism enzymes and their regulators (namely fumarate hydratase, respiratory complex I and PGC1) in the modulation of both metabolic and epigenetic profiles triggering tumor progression and chemoresistance. Finally, the decrease in cancer cells growth was reported by using cell permeable αKG ester analogues, ROS prevention and ketogenic diet. These potential metabolic-based anticancer strategies were proved in vitro (2D and 3D cancer cell models) and in vivo (xenografts in immunodeficient mice).
2) to implement innovative technologies and integrated methodologies in the field of mitochondrial physiopathology to dissect the molecular mechanisms underlying cancer. This activity led TRANSMIT to develop and exploit different in vitro and in vivo solid cancer models with different hystotypes. In particular, 2D and 3D cancer cells models were developed and improved. Cancer cell lines lacking of pivotal oxidative enzymes using genome editing were generated and characterized. These models were also used to develop xenografts in immunodeficient mice. Further, the use biochemical, metabolomic, proteomic and bioinformatic integrated technologies allowed TRANSMIT to evaluate the bioenergetic, metabolic and epigenetic rewiring in several solid cancer models and define the mitochondria as hub to sustain cancer cell survival and proliferation.
3) to provide a full portfolio of complementary skills through the creation of a network of basic, translational and industrial laboratories. First, this activity exposed ESRs to a multidisciplinary/multisectorial industrial field allowing them to learn how to design and produce cancer-related tools as commercially exploitable output. Then, the interaction with Associate partners such as FUV and Dynamo Camp sensitized ESRs towards both scientific dissemination and fundraiser. Indeed, ESRs were personally involved in organizing the patients Symposium and a crowdfunding campaign. These two dissemination activities tightly connected with the research training markedly impact on the scientific oncological community, as well as on the patients, their families, the international patients’ associations and the entire society.
