NOVEL ANTICANCER THERAPIES

Degree course: 
Corso di Second cycle degree in BIOMEDICAL SCIENCES
Academyc year when starting the degree: 
2019/2020
Year: 
1
Academyc year when helding the course: 
2019/2020
Course type: 
Compulsory subjects, characteristic of the class
Language: 
English
Credits: 
6
Period: 
Second semester
Standard lectures hours: 
56
Detail of lecture’s hours: 
Lesson (40 hours), Exercise (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

The final exam consists of an oral interview (about 30 minutes in duration) on any topic selected from the syllabus. The quality of the oral presentation will be evaluated and graded (A= highest, C=lowest) based on Synthesis, Clarity and Ability to discuss; students will also be asked to present their notes from the practical experiences and these will be evaluated and graded (A= highest, C=lowest 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 (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.

Assessment: 
Voto Finale

The course is designed to provide an updated overview of the molecular and cellular mechanism(s) of action (and resistance) of novel approaches to the clinical management of cancer, that are increasingly associated with, and in some case have replaced, conventional cytotoxic chemotherapy. Students will become familiar with endocrine, antiangiogenic and immunotherapeutic agents, as well as the very recent strategies based on engineering of autologous or allogeneic cells; they will learn about the experimental models and tools that lead to the discovery of new strategies and drug targets. Their practical skills will be honed in a companion laboratory module, whereby they shall learn how to plan and perform different experiments, how to correctly interpret experimental results and how to effectively summarize their lab activity by writing a clear and concise report. The student’s communication skills and their ability to work in a team will be challenged during interactive discussion in class and through the preparation of an oral presentation that will be presented and discussed at the end of the course in front of the teacher and of their classmates, on topics selected from the syllabus’ contents.

1. Principles of targeted therapies.
2. Successful targeted therapies in the clinic
3. Other (more or less) successful targeted approaches
4. Immunotherapies
5. Antiangiogenic therapy
6. Endocrine therapy for breast and prostate cancer
7. Novel concepts in the development of anticancer drug therapies

Practical module: pharmacological modulation of cancer cell migration

1. Principles of targeted therapies.
2. Successful targeted therapies in the clinic
2.1 Agents used in the management of chronic myeloid leukemia and gastrointestinal stromal tumors
2.2 Agents used in the management of acute promyelocytic leukemia
2.3 Agents used in the management of non-small cell lung cancer
2.4 Agents used in the management of metastatic melanoma
3. Other more or less successful targeted approaches
3.1 PARP inhibitors
3.2 Cell cycle inhibitors
3.3 Epidrugs
3.4 Agents targeting the proteasome
3.5 Agents targeting the PI3K-Akt-mTOR pathway
3.6 The p53 angle
4. Immunotherapies
4.1 Therapeutic antibodies and their “congeners”
4.2 Immunomodulators
4.3 Immune checkpoint inhibitors
4.4 Cell-based therapeutics
5. Antiangiogenic therapy
6. Endocrine therapy for breast and prostate cancer
7. Novel concepts in the development of anticancer drug therapies
7.1 Targeting the tumor microenvironment
7.2 Targeting the tumor metabolism
7.3 Targeting cancer-initiating 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.

TESTI DI RIFERIMENTO
Lectures and the accompanying visual materials are the major source of information for the student. Thus, consistent attendance is recommended. 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. Students are also encouraged to autonomously investigate aspects of special interest, by critically searching the literature and the Internet.
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

Convenzionale

The course consists of ex cathedra lectures but aims at creating a direct interaction between students and teacher, in order to stimulate the students' interest in the topics of the course. Some of the listed topics will be selected for presentation by the students in the final part of the course; such topics are an integral part of the program and may be the object of the final interview
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.

Prof. Monti will receive the students by appointment 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.