- Docente: Giuseppe Gasparre
- Credits: 1
- SSD: MED/03
- Language: Italian
- Teaching Mode: Traditional lectures
- Campus: Bologna
- Corso: Single cycle degree programme (LMCU) in Medicine and Surgery (cod. 8415)
Learning outcomes
Students will become familiar with the biochemical and mitochondrial pathways that become modified during neoplastic transformation and cancer progression, including the metabolic reprogramming at the level of the metastatic niche.
Course contents
Generalities of cancer metabolism.
Definition of neoplasia, basic concepts of cell transformation. Cancer as a genetic disease. Branched Darwinian evolution of cancer. Gene classes involved in cancerogenesis. Hallmarks of cancer and relevance of metabolic reprogramming. Warburg's observations, aerobic glycolysis and seminal hypotheses. Key metabolites in cancer cells. Physiological vs. interrupted Krebs cycle and anaplerosis. Carbon fluxes: pyruvate; citrate and its destiny; glutamine and glutaminolysis in both the aerobic and the anoxic mode. Waves of metabolic reprogramming. The central role of mitochondrial biogenesis, its stimuli and coactivators (PGC). Retrograde signaling between mitochondria and nucleus.
Oncogenes, tumor suppressors and their metabolic role.
Mitochondrial enzymes as tumor suppressor genes: paragangliomas and SDH mutations; leyomiomas and FH mutations; gliomas and IDH mutations. Metabolic consequences: role of HIF1 and pseudohypoxia. Epigenetics and oncometabolites: regulation of ketoglutarate-dependent dioxygenases.
Metabolism in the metastatic niche.
Epithelial-mesenchymal transition and links with cell metabolism. Brain, lung, liver, bone and omentum metastases and their metabolic features, including organ mimicry to evade the immune system.
Readings/Bibliography
Tumor Cell Metabolism: Pathways, Regulation and Biology. Springer.
Mitochondria and cancer. Wallace DC. Nat Rev Cancer. 2012 Oct;12(10):685-98. doi: 10.1038/nrc3365.
Mitochondrial mutations in cancer. Brandon M, Baldi P, Wallace DC. Oncogene. 2006 Aug 7;25(34):4647-62. Review.
Mitochondria and cancer: Warburg addressed. Wallace DC. Cold Spring Harb Symp Quant Biol. 2005;70:363-74. Review.
A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Wallace DC. Annu Rev Genet. 2005;39:359-407. Review.
Complex I impairment in mitochondrial diseases and cancer: Parallel roads leading to different outcomes. Iommarini L, et al. Int J Biochem Cell Biol. 2012 Jun 2.
Learning from oncocytic tumors: Why choose inefficient mitochondria? Gasparre G, et al. Biochim Biophys Acta. 2011 Jun;1807(6):633-42. Epub 2010 Aug 21. Review.
A global view of the biochemical pathways involved in the regulation of the metabolism of cancer cells.Icard P, Lincet H. Biochim Biophys Acta. 2012 Dec;1826(12):423-33. doi: 10.1016/j.bbcan.2012.07.001.
Teaching methods
Up-front lectures with power point slides presentations. The class will be invited to talke active part in the discussion of issues raised during the lectures.
Assessment methods
Multiple choice test. The test poses 6 different questions with three possible answers one of which only is correct. The test is passed by answering correctly to three of the six questions.
No mark is foreseen for this optional course. Pass or not pass will be awarded according to the result of the final examination.
Teaching tools
Powerpoint slides
Scientific papers
Teaching material will be provided at the end of each class on the on line platform. Textbooks and papers are not considered compulsory readings.
Office hours
See the website of Giuseppe Gasparre