LMP420H1 – Cancer Pathogenesis

Course description

This course includes a rather broad domain of molecular, genetic,
cellular, physiological, clinical and etiological aspects. These overlap with social and environmental domains that further inform our understanding of cancer.

A course in one term of the academic year will necessarily have limitations in the depth and breadth in considering the current understanding of the various pathways and processes in cancer biology.

The orientation that we will use will rely heavily on the "Hallmarks of Cancer" as a central framework to understand the pathobiology of cancer. We will also consider a number of etiological aspects that interact with this framework, including genetic and environmental aspects of cancer.

We will also consider how these processes and mechanisms can be used for intervention in this broad collection of maladies.

We will be concerned primarily with the "nature of cancer" at mechanistic levels (molecular, genetic, cellular and physiological) leading us to consider at least some approaches to selectively eliminate transformed cells or mitigate their deleterious consequences.

Course coordinators

Dr. George Charames

Office address: Sinai Health, 700 University Ave, Room 8-400-6-3 

Dr. Paul Hamel

Office address: 1 King’s College Circle, MSB Rm 6316

Teaching assistant

Negar Khosraviani



Winter 2024

Lecture time

Thursday 10 am - 12 pm 

Tutorial time

Thursday 12 - 1 pm

Office hours

Contact TA or Course Coordinators

Course details

  • Hours: 24L/12T
  • Prerequisite: LMP310H1
  • Exclusions: None
  • Recommended preparation: PCL386H1
  • Distribution requirements: Science
  • Breadth requirement: Living Things and Their Environment (4)          
  • Enrolment limits: 35 students

Student evaluation

Assessments for this course will be discussed and decided with the class during the first session.  

Typically, assessments are based primarily on presentation of papers and participation during class. There is likely to be at least one writing exercise during the term.  

Late work is not accepted in this course with the exception reasons outlined in the University of Toronto Missed Assessment Policy.

See information on Academic Integrity


Lecture topics are subject to change. See below for lecture descriptions.




11 January, 2024

Welcome to LMP420: Pathophysiology and Global Scope of Cancer


18 January, 2024

Hallmarks of Cancer and Oncogenic Pathways


25 January, 2024

Viruses and Cancer Stem Cells


1 February, 2024

Sustaining Proliferative Signalling


8 February, 2024

Evading Growth Suppressors


15 February, 2024

The Immune System: Avoiding Immune Destruction & Tumour Promoting Inflammation


29 February, 2024

Enabling Replicative Immortality and Resisting Cell Death


7 March, 2023

Activating Invasion and Metastasis


14 March, 2024

Inducing or Accessing Vasculature


21 March, 2024

Deregulating Cellular Metabolism


28 March, 2024

Genome Instability and Mutation


4 April, 2024

Precision Cancer Medicine


Recommended reading or text book


How 'lectures' will be structured

While listed as a 'lecture' course, we anticipate that students in this class are in the advanced stages of their undergraduate programs with most being in the last term of their last year. As such, this course will be similar to a graduate seminar course. Rather than 'just lectures', everyone in the course will be active participants in studying and relaying information, models, and approaches to understanding the various aspects of the
pathobiology of cancer.

General structure for Thursday 'lectures'

Each week we will interrogate a specific theme.

Usually there will be a 15 - 20 minute presentation by an academic leader who will orient the class to specific aspects of that theme. These short presentations may include some ideas of the current state of knowledge in a given area.

Following the presentation, generally two different groups of students (2 x 40 minutes each) will then lead the session by presenting primary papers that describe aspects of the particular area of cancer biology under consideration that week. We expect these groups to self-assemble and that each group will make at least two presentations during the term. You will select the essential, illustrative, parts of these papers, as well as including additional materials to further embellish our understanding of a particular aspect of the pathobiology of cancer.

Students not presenting in a given week will be expected to have read the papers and to actively engage in the detailed discussions.

General structure for Friday tutorials

For the Friday tutorial, all the members of the groups presenting during the following week will be required to meet with the TA in the week before their presentations in order to fashion a plan for their presentation and to discuss the specific materials that will be used in that next session.

The materials will be made available to the rest of the class by Tuesday so the class can be prepared for the Thursday session.

These meetings (one, two or three weeks ahead of the specific class in which the presentations will be made) will be coordinated with the TA.

Lecture descriptions

12 January: Welcome to LMP420: Pathophysiology and Global Scope of Cancer

As a basic starting point, we will establish the outlines of the various forms of cancer, their geographical distribution and the temporal changes in cancer incidence.

Some discussion concerning the study of cancer and the myriad intersecting disciplines that inform these investigations will also form part of this session.

19 January: Hallmarks of Cancer and Oncogenic Pathways

In this session, we will consider using the "Hallmarks of Cancer" approach first proposed by Robert Weinberg over three decades ago.

This approach discusses the essential molecular, cellular, and physiological aspects of neoplasms. This approach will be used throughout the course, thus forming one of the core aspects of our deliberations.

Using a number of large-scale, data-rich approaches, we will also begin to appreciate the outlines of the myriad molecular, genetic and cellular pathways that are involved in transformation, growth and metastasis of cancer cells.

As will become evident, while often studied as individual molecules in relatively linear pathways, the pathobiology of cancer
involves complex networks - both within cancer cells themselves and in the supporting stroma.

26 January: Viruses and Cancer Stem Cells

Part one: viruses

While the study of viruses may appear somewhat outside the "Hallmarks of Cancer" framework, their study is relevant to cancer biology on a number of levels.

Historically, they represented one of the first examples of an environmental factor giving rise to neoplasms in animals. More detailed genetic and molecular analyses showed that specific genetic elements were responsible for causing cellular transformation and were essential in the demonstration that normal genetic elements in animals were, in fact, the basis of the oncogenes that caused cellular transformation.

Other varieties of viruses also help define classes of tumour suppressor genes and lead to the discovery that a number of genes important in animal development contribute to cellular transformation.

Part two: Cancer Stem Cells

In the second part of this class, we introduce the Cancer Stem Cell model.

A number of characteristics of stem cells make this a compelling model to understand a variety of phenomena related to the phenotype of cancer cells, the refractory nature of some cancers to therapeutic interventions and the reoccurrence of cancer cells, often with long latency, following apparent remission.

While the subject is introduced here, this model will be important in discussions throughout the course amongst the other themes we cover.

2 February: Sustaining Proliferative Signalling

Sustaining cell proliferation stands out as one of the obvious features amongst the Hallmarks of Cancer.

Here, we will take a (limited) survey of some mechanisms that normally control the cell division cycle. How the control of these mechanisms fail or are subverted to contribute to the transformed phenotype will be the essential aspect of this section.

9 February: Evading Growth Suppressors

Historical cell biology experiments suggested that the transformed phenotype was a "recessive state", suggesting that there exists suppressors of the transformed phenotype.

Now termed growth suppressors these factors are an intensely-studied area and their inactivation by, for example, tumour viruses or by mutational or silencing mechanisms have revealed the importance of "negative" regulators of the cell division cycle and their contributions to cell transformation.

16 February: Avoiding Immune Destruction and Tumour Promoting Inflammation

Transformed cells need to be able to evade immune surveillance. Recent evidence has shown that these cells can can provide a "Don't Eat Me" signal that prevents the innate immune system from using macrophage-mediated phagocytosis to eliminate these cancer cells.

Furthermore, cancer-cell signalling can promote an inflammatory microenvironment that promotes cell growth and/or metastasis. These mechanisms also provide points of intervention where alterations of these signals could be used to block growth or, indeed, lead to immune system-dependent elimination.

2 March: Enabling Replicative Immortality and Resisting Cell Death

In normal human diploid cells, the length of the repetitive guanine rich DNA sequence at the caps of chromosomes, telomeres, shortens with each successive replication cycle.

In the 960s, Leonard Hayflick and his colleagues discovered that once telomeres reach a critical length, they enter a permanent cell cycle arrest. This critical threshold has been termed the “Hayflick Limit.”

Many cancer types have adapted to overcome this limit by lengthening telomeres via telomerase-dependent methods as well as ALT (alternative lengthening of telomeres) mechanisms. 

9 March: Activating Invasion and Metastasis

A hallmark distinguishing feature of cancer cells relative to all other cells in the body is the ability to invade into nearby tissues and migrate to other areas of the body where they can infiltrate and colonize.

The ability for cancer cells to separate from its current environment, transform or dedifferentiate into a stem cell-like state in order to survive in a new microenvironment is often accomplished through loss of E-cadherin (CDH1) and associated with a process called epithelial-mesenchymal transition (EMT), respectively.

16 March: Inducing or Accessing Vasculature

The ability for tumour cells to actively promote the growth of new blood vessels is one of the hallmarks of cancer.

The processes and reciprocal signalling cascades that are involved will be the focus of this session as will the utility of therapeutically-blocking angiogenesis as a strategy for controlling cancer growth. 

23 March: Genome Instability and Mutation

Preservation of the integrity of a cell's collection of genetic information (ie. genome) is managed by numerous processes such as DNA damage repair pathways, epigenetic mechanisms, maintenance of telomere lengths, and the management of repetitive DNA sequences.

Disruption of any of these processes may lead to an accumulation of mutations that lead to carcinogenesis. This concept of genomic instability and associated mutations are the concepts that this unit will explore.

30 March: Deregulating Cellular Metabolism

Cell growth and proliferation requires the import and metabolism of key nutrients e.g. glucose and amino acids such as glutamine) into energy under favourable aerobic conditions and while under metabolic stress (eg. hypoxic environment or low nutrient supply).

Cancer cells demonstrate an upregulation of imported nutrients and alter the rate of metabolism, despite unfavourable conditions. 

6 April: Precision Cancer Medicine – An Overview

Precision Medicine is an emerging approach applied to many diseases.

For cancer, it is most commonly associated using the genomic information within a patient’s tumour to aid in diagnosis, more accurately predict response to treatments, tailor targeted therapies, and possibly serve as eligibility to clinical research trials.