Download Bios E-150: The Biology of Cancer

Jamie Dempsey Barber
Harvard University Extension School
Bios E-150: The Biology of Cancer
Harvard University Extension School
Spring 2016
Course Description
Cancer is defined as uncontrollable cell growth. The complexities of the causes and
the different types of cells that give rise to this disease have underscored the need
for a better understanding of the basic biology of cancer. Advancements in basic
and biomedical research have led to more effective treatments, enhanced detection
methods, and better prevention strategies. This course aims to provide a
comprehensive overview of the biology and pathology of cancer. The first half of the
course will focus on the genetic and molecular basis of cancer. We will explore the
role of mutations in cancer cells, and how they lead to the dysregulation of essential
biological properties like programmed cell death, cell proliferation and
differentiation. The second half of the course will focus on the interface of cancer
and medicine. Classical treatment methods will be compared with newer treatment
strategies like targeted therapies. We will also explore the challenges associated
with diagnosing cancers, as well as ways in which to prevent cancer. The everexpanding role of “omics” and bioinformatics in areas such as tumor classification,
prognosis and treatment will also be discussed.
Prerequisite: Bios E-1a and Bios E-16/W or the equivalent; Bios E-12 recommended.
Overarching Course Objectives
! What are the common cellular and molecular mechanisms that are
deregulated in cancerous cells, and how does their deregulation contribute
to the development of cancer?
! What role does gene mutation play in the development of cancer? In what
ways can cancer be considered a “heritable” trait?
! In what ways do environmental factors influence cancer susceptibility and
how may we use this information to prevent cancer?
! How does cancer manifest itself in the human body? What features of
cancer lead to high mortality rates?
! What is the biological rationale for both traditional chemotherapies and novel
targeted therapeutic approaches? What are the benefits and limitations of
each option?
! In what ways can genomic technologies provide insight into cancer
prevention, diagnosis, and treatment? What are the limitations of these
technologies?
Jamie Dempsey Barber
Harvard University Extension School
Underlying Themes
! Linking of basic science and medicine - how research at the cellular and
molecular level can inform how we treat patients with cancer.
! Technology development - how advances in biomedical technology are
changing the way we think about the underlying causes of cancer and how
we treat it.
Course Instructor
Jamie Dempsey Barber, PhD
[email protected]
Office hours: please arrange time as needed
Course Location
Location TBD
Tuesdays 5:30-7:30p.m. Discussion section will run from 7:35-8:30p.m.
Textbook
Weinberg, Robert A. The Biology of Cancer, Second Edition. New York: Garland
Science, 2013.
Any additional readings, including discussion papers, will be announced
and posted on the course website.
Website
https://canvas.harvard.edu/courses/8460
Please check the course website frequently for announcements and postings.
Jamie Dempsey Barber
Harvard University Extension School
Course Format
There are different requirements for undergraduate and graduate
students. All students will take two midterms and one final
(non-cumulative) exam. All students will also be required to complete
four problem sets during the course of the semester.
Starting on February 2, there is a mandatory weekly discussion
section for graduate students that will focus on the critical reading
and analysis of primary research papers. Each graduate student will
be responsible for leading the discussion of three papers during the
course of the semester. More detailed information regarding the
discussion session format will be provided at the first discussion
meeting. In addition to four problems sets, graduate students are
required to complete a fifth problem set based on the primary research
papers discussed in section.
There is an optional weekly discussion session for undergraduates to
review concepts, address questions, and go over graded problem sets.
Grading Policies
Undergraduate
Graduate
Midterm 1
25%
Midterm 1
25%
Midterm 2
25%
Midterm 2
25%
Final Exam
25%
Final Exam
25%
Section
15%
Problem Sets
25%
Problem Sets
10%
No late assignments will be accepted and no make-up exams will be given.
Jamie Dempsey Barber
Harvard University Extension School
Course Schedule Spring 2014
Date
January 26
February 2
February 9
February 16
February 23
Topics
1.Introduction to the course
2.Cancer Defined
3. History of Cancer
Research
3.Overview of the hallmarks
of cancer
1.Mutagens, carcinogens,
and mutations
2.Tumor viruses and the
discovery of oncogenes
3.Tumor cells possess
genetic abnormalities
1.Mechanisms of oncogene
activation
2.Role of growth factors and
receptors in carcinogenesis
1.RAS signaling in cancer
2.Familial cancer
syndromes and the
discovery of tumor
suppressors
Objectives
What types of cellular
processes go awry in the
transformation of normal
cells to cancerous cells?
What evidence indicates
that tumors arise from
normal tissues in a multistep process?
What is a mutation, and
what are some of the ways
that mutations arise?
What evidence indicates
that cancer is caused by
mutations?
Since cancer is not an
“infectious” disease, in
what ways do viruses
contribute to the cause of
cancer?
What is an oncogene, and
in what ways can a protooncogene be activated?
What are the mechanisms
of growth factor receptor
activation?
In what ways do growth
factor receptors contribute
to cancer?
In what ways can
oncogenic activation of
RAS contribute to the
development of cancer?
What is a tumor suppressor
gene, and how may one
become inactivated?
Why do tumor suppressors
typically function as
recessive alleles, while
oncogenes are usually
dominant?
**Midterm 1**
Readings
Notes
Chapter 1
(review)
Chapter 2.1-2.5
Chapter 11.111.2
Chapter 2.7-2.11
Chapter 3
Chapter 4
Chapter 5.1-5.7
Problem
Set #1 Due
Chapter 6.1-6.7,
6.11-6.14
Chapter 7.1-7.11,
7.13
No sections
Jamie Dempsey Barber
Harvard University Extension School
March 1
March 8
March 15
March 22
April 29
April 5
1.Cell cycle control and the
pRb tumor suppressor
2.Apoptosis and the p53
tumor suppressor
What is the role of pRB in
the cell cycle, and how
does disruption of the cell
cycle contribute to the
development of cancer?
What is the role of p53 in
the regulation of DNA
repair and apoptosis? How
does loss of p53 contribute
to the development of
cancer?
What is cellular
senescence and what
1.Cellular senescence
2.Telomeres, cellular
triggers this cellular
response?
immortalization, and
tumorigenesis
What roles do telomeres
and telomerase play in
normal cells? How are
these roles altered in tumor
cells?
**Spring Break No Class**
How does multi-step
tumorigenesis relate to the
1.Multi-step tumorigenesis
evolution of cancer over
and the evolution of cancer
time?
How do tumor promoting
2.Tumor-promoting stimuli
agents and mutagens differ
3.Cancer stem cells
in their contribution to the
development of cancer?
How are they similar?
In what ways can we utilize
our knowledge of multi-step
tumorigenesis to develop
strategies for the
prevention of cancer?
1.DNA repair mechanisms
2.DNA repair defects and
their relationship to cancer
What are the various
methods of DNA repair,
and why have so many of
these mechanisms
evolved?
How are defects in DNA
repair related to cancer?
**Midterm 2**
Chapter 8.1-8.8,
8.12-8.13
Chapter 9.1-9.12,
9.16
Chapter 10
Problem
Set #2 Due
Chapter 11.311.15, 11.1711.18
Chapter 12
No sections
Jamie Dempsey Barber
Harvard University Extension School
April 12
1.Angiogenesis
2.Metastasis
April 19
1.Tumor Immunology
2.Cancer cell metabolism
April 26
1.Treatmenttraditional
chemotherapeutics
2.TreatmentImmunotherapies
What is angiogenesis, and
why is it critical to tumor
survival?
What types of tumorenvironment interactions
must take place in order for
angiogenesis, invasion,
and metastasis to occur?
How do various antiangiogenic therapies work
in the treatment of cancer?
How is the metabolism of a
resting cell different from a
proliferating cell? What
molecules are important for
the altered cancer cell
metabolism?
What pathways contribute to
the altered cancer cell
metabolism?
What is the rationale
behind conventional
chemotherapy, and what
are some of the drawbacks
to this approach to
treatment?
What evidence suggests
that the immune system
plays a role in suppressing
cancer?
How might our immune
system be exploited to
make tumor cells more
susceptible to
immunologic attack? What
are some of the drawbacks
to this approach?
Chapter 13
Chapter 14
Chapter 15 and
Supplemental
readings
Chapter 15
Problem
Set #3 Due
Jamie Dempsey Barber
Harvard University Extension School
May 3
May 10
1. Treatmenttargeted therapy.
2. New Genomic and
proteomic
technologies
3. Applications of
new technologies
in prevention,
assessing risk,
diagnostics, and
treatment.
How does rational therapy
differ from traditional
chemotherapeutic
approaches? What are the
advantages and
disadvantages to this type
of approach?
What classes of molecules
might be good targets for
the development of new
anti-cancer therapies?
Why may some molecules
be better targets than
others?
**Final Exam**
Problem
Chapter 16 and
Set #4 Due
Supplemental
Readings (to be
provided)
No sections