86359 - Cancer Metabolism

Academic Year 2018/2019

  • Teaching Mode: Traditional lectures
  • Campus: Bologna
  • Corso: Single cycle degree programme (LMCU) in Medicine and Surgery (cod. 9210)

Learning outcomes

The student will become familiar with the concept of cancer heterogeneity related to metabolism, understand genetic, molecular and biochemical mechanisms leading to metabolism-guided cancer resistance, and acquire means of identification of such conditions. The course will describe non-canonical concepts currently emerging in oncology, and associated methodologies for their investigation, which go beyond oncogene/tumor suppressor definitions to explaining cancer insurgence, such as double-faced nature of mutations arising in the same gene, but resulting in opposite effects on the disease outcome.

Course contents

We advice to take the course during the second year. First years may attend provided they have at least a basic knowledge of general biochemistry and molecular biology.

Lesson 1-2. Generalities of cancer metabolism.

Definition of cancer as a genetically-determined disease. Sequential steps of tumorigenesis: initiation, promotion, progression. Evolution of tumors: branched evolution and darwinian aspects. Heterogeneity as a result of clonal expansion and selection due to pressures. Hallmarks of cancer. Importance of cell metabolism in cancer cell reprogramming. Warburg and his observations: the Warburg effect. Carbon fluxes and the main metabolites involved in metabolic reprogramming of cancer. Cell cooperativity and byproducts. The waves of metabolic reprogramming in cancer progression: oncogenic stimuli, hypoxia, aglycemia, mitochondrial revival and biogenesis. The role of biogenesis regulators and their double-edged function in progression. Retrograde signaling for biogenesis activation.

Lesson 2-3. Oncogenes, tumor suppressor genes and their metabolic role.

Mitochondrial tumor suppressor enzymes. Metabolism of HIF1 and its regulation. The role of PHD as oxygen sensors, and other dioxygenases. IDH mutations in glioma and their neomorphic function. Bases of metabolism-dependent epigenetic regulation – the one-carbon metabolism.

Lesson 3. Metabolic changes in the metastatic niches.

The acquisition of metastatic properties: epithelial-mesenchymal transition. Markers of differentiation and links between EMT and metabolism: the role of hypoxia. Metabolic properties acquired by metastases in the different districts: brain, lung, bone, omentum, liver. Dormancy and awakening of therapy-resistant cells.

Lesson 4. Role of mtDNA in cancer.

Mechanisms of mitochondrial DNA (mtDNA) acquisition. Oxidative and Warburg metabolism in the selection of metastatic and therapy-resistant cells. The mitochondrial genome and its features. The role and selection of mtDNA somatic mutations in tumorigenesis. The protumorigenic role: ROS production and loop of mutagenicity, HIF1a stabilization and mitogenic properties. Antitumorigenic effect of oncojanus genes. Oncocytic tumors and their clinical and molecular peculiarities.

Lesson 5. Cooperativity among cells constituting the tumor bulk.

Homogeneity versus uniformity. Components of the cancer mass and mechanisms of cooperation and modalities of relationships among cells. Commensalism, parassitism, symbiosis. Metabolic exchanges according to oxygen and nutrient gradients, and vessel distance. Local and systemic metabolic relations: cachexia and systemic consequences of nutrients redirectioning and organs metabolic changes. The influence of cancer cells on a body level.

Lesson 6. Methodologies in cancer research.

Cancer models: cell cultures, human samples, mouse and animal models. Hypothesis-driven and non hypothesis-driven methods. Tissue analysis, stainings, immunohistochemistry. Immunofluorescence, specific markers search and interpretation. Oncogene expression/repression. Omics approaches. 3D cultures. Single cell analyses. Western blotting for metabolic proteins.

Lessons 7-8. Practicals.

The course also includes 3 to 6 hours of practical activities in the molecular genetics and biology laboratory, at the end of the course: cancer cell culturing and passaging, evaluation of the tumorigenic and invasive potential of cancer cells through scratch (wound healing) assay and colony growth, via colorimetric analysis, and data analysis.

Readings/Bibliography

Tumor Cell Metabolism: Pathways, Regulation and Biology. Springer. ISBN: 978-3-7091-1823-8

Selected scientific article from the literature.

The texts are not compulsory reading. Notes and teaching materials - provided after each class - will be considered sufficient reading. Materials will be provided on the IOL platform.

Teaching methods

Lectures with ppt presentation. Class discussion on case studies and examples from the scientific literature.

The minimum attendance requirement to be admitted to the final exam is 66% of lessons. Students who fail to meet the minimum attendance requirement will not be admitted to the final exam of the course, and these optional 3 credits will not be given.

Professors may authorise excused absences upon receipt of proper justifying documentation, in case of illness or serious reasons. Excused absences do not count against a student’s attendance record to determine their minimum attendance requirement.

Assessment methods

Multiple choice questions.

Students will be given 18 questions with 3 or 4 possible answer each, only one of which correct. Six questions will therefore be asked for each of three main topics listed in the Course Programme.

Pass: Give >60% correct answers (11/18 answers).

No penalty for wrong answers, or answers not given.

No mark is foreseen for this oprional course. Pass or not pass will be awarded according to the result of the final examination.

Teaching tools

PPT slides; scientific articles on the topics dealt with during the course. Textbook (not compulsory).

Office hours

See the website of Giuseppe Gasparre