Periodic Reporting for period 2 - TRANSMIT (TRANSlating the role of Mitochondria in Tumorigenesis)
Reporting period: 2019-01-01 to 2021-06-30
During the project, TRANSMIT investigated the metabolic changes that characterize human cancers, with emphasis on the role of mitochondria, bridging basic research to the improvement/development of therapeutic strategies, and ultimately fostering the communication of this rapidly emerging field of innovative research to the general public.
Further, TRANSMIT fostered the communication of this emerging field to the patients and their families. Thanks to its multi-partners Consortium, TRANSMIT project allowed to transfer the current knowledge into the wide field of cancer research, translating scientific and technical advances into the education and training of eleven Early Stage Researchers in the field of cancer biology.
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.