- Scheda dell'insegnamento
- Obiettivi formativi
- Metodi didattici
- Verifica dell'apprendimento
Knowledge and understanding
At the end of the course, students should be able to:
1. understand and describe the mechanisms of action and resistance and the toxic effects of the major classes of anticancer agents in current clinical use;
2. understand and discuss the strategies that have been used in the past to develop anticancer agents in contrast with the newly developed strategies
3. understand and discuss the basic concepts of oncogene addiction, synthetic lethality, redundancy and feedback circuitries and the impact that may have on therapeutic outcomes.
Applying knowledge and understanding
At the end of the course, students should have developed the ability to effectively to research data in the scientific literature, to synthetize them in a PowerPoint and to competently discuss the presented material.
The laboratory experience will prepare the students to address the more challenging tasks that they will face during their practical training for the preparation of the thesis, providing the basics of sterile cell culture, encouraging teamwork and stimulating critical appraisal of the experimental results.
To fully understand the topics addressed in the present course, students should possess basic notions of cellular biology and pathology and of general pharmacology
1. General principles of anticancer chemotherapy:
1.1. tumor cell growth kinetics; mechanisms of resistance;
1.2. toxic side effects;
1.3. pharmacogenomic issues
2. Cytotoxic Agents:
2.2. microtubule poisons;
2.3. DNA topoisomerase poisons;
2.4. DNA-interacting agents
3. Endocrine therapies e cancer immunoterapy:
3.1. endocrine therapy of breast cancer;
3.2. endocrine therapy of prostate cancer;
3.4. immune checkpoint inhibitors and other immunotherapies
4. Antiangiogenic and antivascular therapies:
4.1. VEGF-targeting agents;
4.2. multikinase inhibitors;
4.3. antivascular agents
5. General principles of targeted therapies:
5.1. oncogene addiction and synthetic lethality;
5.2. therapeutic antibodies versus small molecule inhibitors
6. Clinically approved targeted therapies:
6.1. drugs used in the therapy of chronic myeloid leukemia and gastrointestinal stromal tumors;
6.2. drugs targeting membrane receptors and intracellular signal transduction pathways;
6.3. drugs inhibiting intracellular protein degradation;
6.5. drugs inhibiting cell cycle-dependent kinases
6.6. direct apoptosis-inducing agents
7. Targeted therapies under clinical development:
7.1. pharmacological modulation of p53 function;
7.2. targeting the cell cycle checkpoints
8. Novel concepts in the development of anticancer drug therapies:
8.1. the tumor microenvironment as a potential therapeutic target;
8.2. role of autophagy in tumor development and response to anticancer therapies;
8.3. the epithelial-mesenchymal transition and metastatic dissemination;
8.4. targeting cancer stem cells.
Two laboratory experiences are included in the program of the course, both focusing on pharmacological modulation of cancer cell migration, a prerequisite for metastasis formation. The students will be divided into groups of 6-8, who will attend lab practice during different weeks, and within each group into teams of 2-3, who will operate simultaneously. Experience #1 is based on the wound healing assay, involving 3 steps in 3 different days: day 1- cell harvesting, counting and seeding; day 2 - observation + drug treatment; day 4: observation + data analysis using the T-scratch software for image analysis and the GraphPad Prism software for statistical analysis. Experience #2 is based on a modified Boyden chamber assay and involves 2 steps in 2 different days: day 1 - day 1- cell harvesting, counting and seeding + drug treatment; day 3 - sample processing and data analysis.
The course consists of ex cathedra lectures, but aims at creating a direct interaction between students and teacher, in order to stir the students' interest concerning the topics of the course. The practical module consists of about 12 hours/student of laboratory practice, preceded by an explanation of the principles, purposes and pitfalls of the tests they are going to be performed.
Lectures and the accompanying visual materials are the major source of information for the student. Thus consistent attendance is recommended; students are also encouraged to further investigate aspects of special interest, by critically searching the literature and the Internet.
Students will be divided into teams of 2 and asked to prepare a PowerPoint presentation (25-30 minutes in duration, including the discussion on topics that will be assigned during the first weeks of the course. The presentation will be evaluated and graded (A= highest, C=lowest) based on Synthesis, Clarity and Ability to discuss. The final exam consists of an oral interview (about 30 minutes in duration) on any topic selected from the syllabus. Students will be asked to present their notes from the practical experiences and these will also be evaluated and graded (A to C) based on Clarity and ability to discuss. The final grade obtained in the interview will be affected by the evaluation of the presentation and lab notes as follows: A=+1 point; B=0; C=-1 point.
Top grades ( 29/30), and possibly honors, will only be awarded to students that can demonstrate the ability to identify and discuss the general principles underlying the major therapeutic approaches, and to work out the connections between the various topics of the course.
Students will find the visual materials and articles relevant to the topics presented during the lectures on the Moodle platform, compatibly with the laws on copyright.
Highly recommended reading: Hanahan D & Weinberg RA - Hallmarks of Cancer: The Next Generation. Cell 144:646-674, 2011.
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