86359 - Cancer Metabolism

Course Unit Page

Academic Year 2022/2023

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. Basics 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. Main signalling pathways involved in regulation of cancer metabolism.

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

The role in cancer metabolism of TP53, PTEN, KRAS, BRAF and MYC. Mitochondrial tumor suppressor enzymes SH and FH. Oncometabolites. Mechanism 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.

Lesson 3. Role of mitochondria 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 mtDNA mutations. Oncocytic tumors and their clinical and molecular peculiarities.

Lesson 4. Cooperativity among cells constituting the tumor bulk.

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. Cell cooperativity and byproducts

Lesson 5. Metabolic changes in the metastatic niches.

The acquisition of metastatic properties: epithelial-mesenchymal transition. Markers of differentiation and links between EMT and metabolism. Circulating tutor cells and ROS. Metabolic properties acquired by metastases in the different districts: brain, lung, bone, omentum.

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 3-6 hours of practical activities in the molecular genetics and biology laboratory, at the end of the course: cancer cell culturing and passaging, immunohistochemistry (proliferation index evaluation, cellular microenvironment analysis).


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

Selected scientific articles from the recent literature will be indicated after each lesson.

The texts are not compulsory reading. Notes and teaching materials will be provided after each class and considered sufficient reading.

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 60% 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.

Authorised excused absences possible upon receipt of proper justifying documentation, in case of illness or other serious reasons.

Assessment methods

A written test with 18 multiple choice questions will be given, with only one answer correct. Pass: Give >60% correct answers (11/18 answers).

No penalty for wrong answers or unanswered questions.

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 and the indicated Textbook

Lab bench activities such as cell culture and in vitro tumorigenic assays.

Office hours

See the website of Ivana Kurelac