Università degli studi dell'Insubria

ANTICANCER PHARMACOLOGY

A.A. di erogazione 2018/2019
Insegnamento obbligatorio

 (A.A. 2018/2019)
Anno di corso: 
1
Tipologia di insegnamento: 
Caratterizzante
Settore disciplinare: 
FARMACOLOGIA (BIO/14)
Crediti: 
6
Ciclo: 
Secondo Semestre
Ore di attivita' frontale: 
56
Dettaglio ore: 
Lezione (40 ore), Laboratorio (16 ore)

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 will describe the molecular mechanism of action and resistance of cytotoxic and targeted anticancer 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 2-3 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.

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:
2.1. 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 affecting cell cycle progression;
6.6. direct apoptosis-inducing agents;
6.7. drugs acting on DNA repair mechanisms;
7. Novel concepts in the development of anticancer drug therapies
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.

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 marks (equal to or greater than 28/30), 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.
Robert A. Weinberg. The Biology of Cancer, 2nd edition, 2013, Garland Science

Prof. Monti will receive the students on Mondays between 2:00 and 4:00 p.m. in her office in Busto Arsizio (Via L. Manara, 7); appointments should be scheduled by e-mail (elena.monti@uninsubria.it). During the course, she will also be available for 30 minutes after each lecture.

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