MBP 1018Y: ONCOLOGY

Wednesdays, 10 a.m. – 12 pmJanuary 6 – April 29, 2016

Princess Margaret Cancer Centre, Room 7-605

OUTLINE Introductions Course Contact Information Course Overview - Goal, Format Course Schedule Course Evaluation Term Project – Midterm Assignment, Term

Paper and Oral Presentation Significant Dates

INTRODUCTION Name Research area Objective for attending this class Personal tidbit you would like to share

CONTACT INFORMATION Course Coordinator: Dr. Michael Reedijk

Email: michael.reedijk@uhn.ca

Teaching Assistant: Megha Kumar (Day-to-day contact person) SLRI, Room 9-983 Tel: 416-586-4800 Ext. 2417 Email: meg.kumar@mail.utoronto.ca

COURSE GOALS To expose graduate students to the

concepts of translational oncology (“from bench to bedside”) through a series of seminar-type presentations highlighting recent advances of translational research

And, To motivate graduate students to apply the

concepts of translational oncology to their own research through a series of written and oral assignments.

CLASS FORMAT Didactic lecture, led by experts in the field,

45-50 minutes in length; followed by discussion/Q&A

Class discussion on 2-3 papers chosen by lecturer, led by students (“Journal Club”-1hr)

COURSE SCHEDUDULEDate Title SpeakerJanuary 6, 2016 Introduction Megha KumarJanuary 13, 2016

Imaged based monitoring of individual response to treatment Greg Czarnota

January 21, 2016 The importance of genetic variation in oncology Geoffrey Liu

January 27, 2016

Novel models and methods for assessment of new targeted agents in oncology David Hedley

February 3, 2016 How to make a biomarker Hel Berman

February 10, 2016 Epigenetic modifications as therapeutic targets Daniel De

Carvalho February 17, 2016 Cancer Immunotherapy Linh Nguyen

February 24, 2016 Liquid Biopsies Scott Bratman

March 2, 2016 Towards personalized epigenomics Mathieu Lupien

March 9, 2016 Lung cancer genomics and patient individualization Ming Tsao

March 16, 2016 Tumor microenvironment and metabolism in radiation oncology Mike Milosevic

March 23, 2016 Novel targeted drugs and their introduction in the clinic Albiruni Razak

March 30, 2016 Novel targets in leukemia Mark MindenApril 6, 2016 Proposal presentations - part 1April 13, 2016 Proposal presentations - part 2April 29, 2016 Final assignment due

JOURNAL CLUB FORMAT All students are expected to read the

assigned papers in advance of the class 2-3 students will be assigned to lead the

journal club discussion in class Come to the session with prepared questions

and/or discussion topics that arise from the selected manuscripts

Be creative with the discussion period! Leaders can feel free to coordinate with each other and develop ways to engage their fellow students and the lecturer in discussion

DO’S Focus on “big picture” – implications of the

papers; integration with earlier concepts in the course; impact on personalized medicine; what comes next?

Engage all students in the discussion Spread the facilitation duties among the

team Keep discussion lively and interesting Critical Analysis

HOW DO WE KEEP THE DISCUSSION GOING? Facilitate! Be creative

Mock debates (pro/con) Play games with the audience Snap group discussions …The sky’s the limit

For advice and assistance, contact me

DO NOT’S Rely only on Powerpoint presentations Dissect/critique the papers, figure by figure Monopolize the discussion Fail to engage your classmates Go over-time

COURSE EVALUATION Participation (20%)

Class attendance (if you are unable to attend with reason, please notify me in advance)

Leadership of journal club Participation in journal club

Midterm Assignment (15%) Oral Presentation (15%) Term Paper (50%)

LECTURE ATTENDANCE MANDATORY If you are unable to attend (for e.g., ill;

committee meeting; conference), please notify me “My experiment got in the way” is not an

acceptable excuse (speaks to time management skills)

“I needed to finish my assignment for X course” is also not an acceptable excuse

TERM PROJECT Group-developed project - grant application

Midterm: Individual letters of intent Oral: Group presentation of project proposal Final: Group project proposal

In these types of grants, often three to four linked initiatives are submitted as part of a larger overall research. For example, a project in head and neck cancer may

involve biomarker identification and validation; imaging; and new therapy development, all linked by common themes and integrated with one another.

Demonstrates “team science” and the ability to integrate concepts and ideas in a collaborative environment

TERM PROJECT Groups of 3-4 Each group identifies an overall topic or

theme MUST be approved by me No two groups can do the same topic Topic choice is made on a first come-first served

basis What’s a topic/theme? Examples:

A given tumor site Multiple approaches to biomarker

discovery/validation Novel target discovery/experimental therapeutics Combinations of the above Anything you can think of!

MIDTERM ASSIGNMENT “Letter-of-intent”/Statement of Research

Interests INDIVIDUAL SUBMISSION 2 pages Single spaced Not including any necessary references or the title

page Contents

Clearly stated research question Well-defined hypothesis Two clearly-stated aims/objectives Translational relevance/Human impact Integration with overall group project

“Set the Stage” for your final assignment

MIDTERM ASSIGNMENT What is NOT necessary

Detailed methodology Discussion of experimental plan

DO NOT make this about your research directly!

To verify this, we ask for a copy of your research abstract (e.g., your project proposal abstract from your first committee meeting or qualifying/reclassification exam; or your student seminar abstract)

Failure to abide by this rule will result in an automatic failing grade in the course; there will be no opportunity for a make-up assignment

You may stay within the same disease, but you must choose a different aspect of it (for e.g., if you are working on a particular signaling pathway, you cannot do that, but you can do something based on imaging modalities in the same disease, or experimental therapeutics, etc.)

You cannot work on the same protein You may apply a technique you’re learning or working on currently

to your research question, but remember that a research question isn’t based around a technique

You can, also, if you like, extrapolate from your research if it is very basic, and consider how you would apply it 5 or 10 years from now, in the clinical setting

If you have any questions, please do not hesitate to contact me

MIDTERM ASSIGNMENT: RESEARCH PLAN “Set the Stage”

Background of your question Clinical and translational relevance Rationale for your choice What models and systems will you be using

You may outline your proposed study design, but don’t make this the focus of your discussion

MIDTERM ASSIGNMENT: RESEARCH PLAN Why are we making you do this?

Experience with a different style of scientific writing Grad students, post-docs and people applying for

faculty positions have to write these statements of research interest in applying for fellowships/positions

Write for a general audience – OK to be nontechnical

Good practice to solidify your ideas before launching into the more complex – and technical – grant writing exercise

ORAL PRESENTATION Group (20-25 minute) oral presentation

outlining your research proposal Focus on translational aims and impact “Interview” for grant proposal

TERM PAPER “Medical Biophysics Translational Research

Grant” Full research proposal

4 pages per group member Single spaced Not including figures, tables, references, title page

This grant is to be built around the translational research aim(s) you designed for the Midterm Assignment

TERM PAPER Longer and more complex than the

midterm assignment Similar to grant and fellowship proposals you will

be writing as a graduate student Similar to the design for a reclass/qualifying exam

proposal Intended to give you a sense of the form and

function in a scientific proposal Meant to be a “window into your thought

processes” if well written

TERM PAPER Components

Abstract of overall project (1 page) Introduction and statement of relevance (2 pages) Rationale and outline of objectives/hypotheses (1

page) Each group member’s specific research proposal

(4 pages, max, each – including a review of preliminary data from the literature, 2 aims, and a statement of translational implication)

A section on integration and an overall conclusion (1 page)

WHAT IS TRANSLATIONAL RESEARCH? For the purposes of this grant, “Translational

Research” is defined to be use of clinically obtained samples in at least one major aim of the proposal

Specifically, use of: Human subjects (with malignancy or disease) Primary tissues/fluids (e.g., bone marrow samples or

tumour biopsies) derived from patients with malignancy or disease

Cell lines derived from patients Patient-derived animal models

BUT I DON’T DO TRANSLATIONAL RESEARCH!

Don’t worry! Fewer of us than you might think do purely translational research

Objective of MBP 1018 is to develop your ability to conceive of and integrate translational concepts into your thinking

If you do: Basic research (with cell lines or animal models) Structural research Photonics or imaging research

…There are translational applications in the future – just think about them!

BUT I DON’T DO ONCOLOGY RESEARCH! That’s OK – think about the pathways you

work on. Do they have application to cancer in some

way? Can you draw connections outside of your

own immediate sphere of research? If you can, write about those connections.

SIGNIFICANT DATES January 6 - Introductory session January 20 - Submission of abstract of term

project; groups identified and topics selected February 3 - Submission of midterm

assignment March 1 - Last date to drop Y/S courses

without academic penalty March 30 - Last session April 6 - Oral presentations – part 1 April 13 - Oral presentations – part 2 April 29 - Submission of term paper

PERSONALIZED MEDICINE

Personalized medicine is an emerging practice of medicine that uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of disease.

BENEFITS1. Early and accurate diagnosis2. Better treatment options3. Minimizing side effects4. Assisting in treatment plans and avoiding

unnecessary treatments; analyzing markers associated with disease progression, response to therapy and relapse.

5. Accurate selection of patients for clinical trials.

6. “Rescue” a failed drug.

CHALLENGES1. Reliable high quality genetic testing

(Guidelines, test optimization and standardization).

2. False positive results3. Cost of screening tools4. Extracting meaningful information from

multilevel analyses and translating into the clinic

5. Interpatient and intratumour heterogeneity and ethnic variation.

6. Secondary genetic mutation