ANTICANCER PHARMACOLOGY

Degree course: 
Corso di Second cycle degree in BIOMEDICAL SCIENCES
Academyc year when starting the degree: 
2017/2018
Year: 
1
Academyc year when helding the course: 
2017/2018
Course type: 
Compulsory subjects, characteristic of the class
Credits: 
6
Period: 
Second semester
Standard lectures hours: 
56
Detail of lecture’s hours: 
Lesson (40 hours), Laboratory (16 hours)
Requirements: 

To fully understand the topics addressed in the present course, students should possess basic notions of cellular biology and pathology and of general pharmacology

Final Examination: 
Orale

Students will be divided into teams of 2 and asked to prepare a PowerPoint presentation (25-30 minutes in duration, including 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 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 (equal to or greater than 29/30), and possibly honors, will only be awarded to students who have participated in discussions during the course and 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.

Assessment: 
Voto Finale

The course is designed to provide an updated overview of the molecular mechanism(s) of action and resistance of anticancer agents in clinical use, including conventional cytotoxic and newer targeted agents. Strategies and targets for the discovery and development of novel anticancer drugs will be highlighted.
Some topics selected from the syllabus will be assigned to the students who, in teams of 2 students each, will prepare an oral presentation that will be presented and discussed at the end of the course in front of the teacher and of their classmates. The topics that are the object of students' presentations are also part of the course program.
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 presentation 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.

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:
2.1 antimetabolites;
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;
3.3 immunomodulators;
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;
6.4 epidrugs;
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.

Practical module
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 - cell harvesting, counting and seeding + drug treatment; day 3 - sample processing and data analysis.

Reference textbook:
Robert A. Weinberg, The biology of Cancer, 2nd edition, 2013, Garland Science
Highly recommended reading:
Hanahan D & Weinberg RA - Hallmarks of Cancer: The Next Generation. Cell 144:646-674, 2011.
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.

The course consists of ex cathedra lectures, but aims at creating a direct interaction between students and teacher, in order to stimulate students' involvement. 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 that 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 referring to recommended textbook and articles and by critically researching the literature and the Internet.

Prof. Monti will receive the students by appointment, to be scheduled by e-mail (elena.monti@uninsubria.it).