Cancer MB&B 323
Instructor: Alexia Belperron
Brief Description: an introduction to cancer with a focus on genetics, biochemistry,
immunity, infection agents, and the associated challenges to prevention and treatment.
Format: The course will be conducted as a seminar, interspersing the presentation of
material by the instructor with frequent opportunities for discussion. There will also be
in depth discussion on research papers throughout the semester. The course will meet
twice weekly.
Learning objectives: The main purpose of the course will be the development of an
understanding of the biology of cancer: including gaining an understanding of normal cell
cycle biology and the genetic changes involved in converting a normal cell into a
cancerous cell, the roles carcinogens, inherited genetic mutations, and infectious diseases
play in the development of cancer, how the immune system responds, and how it can be
harnessed for treatment, the biochemistry of chemotherapy, and the biology underlying
preventative measures. Throughout the course, the emphasis will be on understanding
the core biological principles and how an understanding of these principles is essential to
understanding how cancer develops, how it can be treated, and how we can try to prevent
its development. The class will focus on a subset of cancers as examples, including
leukemias, skin cancer, and those linked to infections.
Grading will be based on the performances on an in-class 80-minute midterm given in
week 8 (33%), 3 quizzes given during weeks 4,7 and 13 (7% each), a group presentation
in the second half of the semester (20%), Journal Club presentation (16%), and overall
class participation (10%).
Group Presentation: Four groups, with ~5 students each, will prepare 40-minute
presentations on a specific cancer (colon, breast, prostate, or lung). They will be
asked to cover topics including, development of disease, risk factors and
treatments and offer suggestions for future uses or research on the topic and how
that would benefit the cancer field. Afterwards there will be a question and
answer period during which other students and the instructor will ask questions of
the presenters. The purpose is to get students thinking in-depth about how they
might apply the knowledge they have gained in the class to understanding
different types of cancer.
Journal Club: Two to three students will work together to present and explain the
data reported in the articles we will be reading throughout the semester. Students
will give an overview of the paper to the class, and then explain the experiments
that were done in each of the figures.
Texts
Cancer: A Beginners Guide, Paul Scotting. London: Oneworld Publications, 2010. ISBN
10: 1851687556.
Supplemental Materials
Understanding Leukemias Lymphomas and Myelomas, Tariq Mughal, John, Goldman,
and Sabena Mughal. London: Taylor & Francis Group, 2006. ISBN1841844098.
Cancer Cell Metabolism and Cancer Treatment, Aurel Lupulescu. Australia: Harwood
Academic Publishers, 2010. ISBN 905702604X.
Primary articles from Nature, and other peer-reviewed journals.
Online Sources including those of the NCI, the ACS, and Cancerquest.
http://www.nature.com/nm/journal/v17/n3/full/nm.2311.html: Taming the dragon:
genomic biomarkers to individualize the treatment of cancer. Nature Medicine 17, 304312, 2011.
http://www.nature.com/nm/journal/v17/n3/full/nm.2328.html: Why don't we get more
cancer? A proposed role of the microenvironment in restraining cancer progression.
Nature Medicine 17, 304-312, 2011.
http://www.nature.com/nm/journal/v17/n3/full/nm0311-296.html: Timeline: a decade of
advances in immunotherapy. Nature Medicine 17, 296, 2011.
http://www.nature.com/nm/journal/v17/n3/full/nm0311-283.html: Targeting the missing
links for cancer therapy. Nature Medicine 17, 283-284, 2011.
http://nobelprize.org/educational/medicine/2001/cellcycle.html
http://www.cancerquest.org/save-the-surfer-home
http://www.cancerquest.org/know-the-flow-home
http://www.sciencemag.org/content/318/5853/1108.full The Genomic Landscapes of
Human Breast and Colorectal Cancers. Science Vol. 308, 1108-1113, 2007 (In this paper,
try to understand the big picture, not the technical details)
http://www.jci.org/articles/view/28607?search%5Barticle_text%5D=papillomavirus&sea
rch%5Bauthors_text%5D=schiller . Prophylactic human papillomavirus vaccines. JCI
Vol 116, 1167-73, 2006
http://www.ncbi.nlm.nih.gov/books/NBK27104/ Using the immune response to attack
tumors
http://www.pnas.org/content/108/38/16032.full
Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission
machinery to induce host cell death. PNAS September 20, 2011 vol. 108 no. 38 1603216037
http://www.sciencedirect.com/science/article/pii/S0092867411003783
nucleotide Deficiency Promotes Genomic Instability in Early Stages of Cancer
Development, Cell, Volume 145, Issue 3, 29 April 2011, Pages 435-446
http://www.sciencedirect.com/science/article/pii/S1535610811001607
Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly Activate Myeloid Cell PI3Kγ,
A Single Convergent Point Promoting Tumor Inflammation and Progression, Cancer
Cell, Volume 19, Issue 6, 14 June 2011, Pages 715-727
http://www.nature.com/nm/journal/v17/n7/full/nm.2390.html
Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures
established tumors. Nature Medicine, 17, 854-859, 2011.
http://www.pnas.org/content/105/44/16958.full.pdf+html
Inhibition of Thr-55 phosphorylation restores p53 nuclear localization and sensitizes
cancer cells to DNA damage, PNAS vol 105, no. 44, pages 16985-16963, 2008.
Jan 31**:
Session 1 Introduction to cancer
Goals: Students will learn about the sizable burden cancer places on the
world’s population and get a preview about the complexities of the
biology, evasive strategies, and adaptive evolution that different cancers
exhibit.
Reading: Cancer: Beg. Guide-Introduction and Chapter 1
Feb 2,7:
Sessions 2-3* Genes: From DNA damage to cancer
Goals: The cell cycle will be reviewed, and students will learn how DNA
damage leads to disregulation of the cell cycle and subsequent
development of tumors. They will learn about the difference between a
tumor suppressor and an oncogene.
Reading:
Cancer: Beg. Guide-Chapters 2-5, Appendices 1-2
http://nobelprize.org/educational/medicine/2001/cellcycle.html
(online cell cycle game)
http://www.cancerquest.org/know-the-flow-home (you should
complete the 1) cell structure, 2) mutation, and 3) oncogene flows)
* Tues, 2/7: Journal Club Paper discussion: Prof Belperron will lead
http://www.nature.com/nm/journal/v11/n1/suppinfo/nm1173_S1.ht
ml
Role of K-ras and Pten in the development of mouse models of
endometriosis and endometrioid ovarian cancer, Nature Medicine,
Vol. 11(1) pages 63-70, 2005.
Feb 9,14:
Sessions 4-5* Carcinogens
Goals: Students will learn about how carcinogens lead to the development
of cancers with a focus on skin cancer.
Reading:
http://www.nature.com/nm/journal/v17/n3/full/nm.2328.html:
Why don't we get more cancer? A proposed role of the
microenvironment in restraining cancer progression. Nature
Medicine 17, 320-29, 2011.
Cancer: Beg. Guide-Chapters 6-7.
http://www.cancerquest.org/save-the-surfer-home (complete the
quiz)
*Tues, 2/14 Journal Club Paper discussion: 1st group student leaders
http://www.sciencedirect.com/science/article/pii/S0092867411003
783
Nucleotide Deficiency Promotes Genomic Instability in Early
Stages of Cancer Development, Cell, Volume 145, Issue 3, 29
April 2011, Pages 435-446
Feb 16:
Session 6Quiz and Genetic predisposition/inherited cancer risks
Goals: Students will learn about the role hereditary mutations play in the
risk of developing cancer
Reading: Cancer: Beg. Guide-Chapters 9-11, Appendix 4
Feb 21:
Session 7* Genetic Analysis of tumors
Goals: Students will learn about different gene expression profiles of
cancers and how biomarkers can be used to diagnose, determine
treatment, and determine the evolutionary origins of the cancer within the
body.
* Tues. Journal Club Paper discussion: 2nd group student leaders
http://www.nejm.org/doi/full/10.1056/NEJMoa041588#t=article
A Multigene Assay to Predict Recurrence of Tamoxifen-Treated,
Node-Negative Breast Cancer. NEJM Vol 351, 2817-26, 2004
Reading : http://www.sciencemag.org/content/318/5853/1108.full
The Genomic Landscapes of Human Breast and Colorectal
Cancers. Science Vol. 308, 1108-1113, 2007
http://www.nature.com/nm/journal/v17/n3/full/nm.2311.html:
Taming the dragon: genomic biomarkers to individualize the
treatment of cancer. Nature Medicine 304-312, 2011
Feb 23,28
Sessions 8-9* Infectious diseases and their role in cancer
Goals: Students will learn about the role different infectious agents play in
the development of cancer
Reading: Cancer: Beg. Guide-Chapter 8
http://www.jci.org/articles/view/28607?search%5Barticle_text%5
D=papillomavirus&search%5Bauthors_text%5D=schiller .
Prophylactic human papillomavirus vaccines. JCI Vol 116, 116773, 2006
*Tues., 2/28 Journal Club Paper discussion: 3rd group student leaders
http://www.pnas.org/content/108/38/16032.full
Helicobacter pylori vacuolating cytotoxin A (VacA) engages the
mitochondrial fission machinery to induce host cell death. PNAS
September 20, 2011 vol. 108 no. 38 16032-16037
.
March 1,6:
Sessions 10-11* Biology of immune responses and how the immune
system responds to tumors:
Goals: Students will learn the basics of immunology needed to
understand the role the immune system plays in surveillance and tumor
control
Reading: Course Packet: How the Immune System works,
Chapters 1,4,5, and 11
Chapter 53 - Cancer and the Cellular Immune Response (Online
source)
*Tues., 3/6 Journal Club Paper discussion: 4th group student leaders
http://www.sciencedirect.com/science/article/pii/S1535610811001
607
Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly Activate
Myeloid Cell PI3Kγ, A Single Convergent Point Promoting Tumor
Inflammation and Progression, Cancer Cell, Volume 19, Issue 6,
14 June 2011, Pages 715-727
March 8:
Session 12Quiz and cont. of immune responses to tumors:
Reading: http://www.ncbi.nlm.nih.gov/books/NBK27104/ Using
the immune response to attack tumors
March 27:
Session 13 Cancers of the immune system
Goals: Students will learn about the development of leukemias and
lymphomas
Reading: Understanding Leukemias Lymphomas and Myelomas,
Tariq Mughal, John, Goldman, and Sabena Mughal. London: Taylor
& Francis Group, 2006. ISBN1841844098-Chap. 3 pgs 27-46.
March 29:
Sessions 14 Treatment tactics: Treatments-past and present
Goals: Students will get an overview about the different approaches used
to treat cancer and will be asked to think about the ways they would
choose to target the disease based on what they have learned about its
biology. This discussion will serve as a review for the midterm.
April 3:
Session 15 In-class midterm
April 5,10:
Session 16-17* Treatment tactics: Chemotherapy
Goals: Students will learn the basic biochemistry of several
chemotherapeutic drugs with broad usage in different cancers and will
learn about the cellular pathways the drugs are designed to inhibit.
Reading: Cancer: Beg. Guide-Chapter 12
* Tues, 4/10 Journal Club Paper Discussion: 5th group student leaders
http://www.pnas.org/content/105/44/16958.full.pdf+html
Inhibition of Thr-55 phosphorylation restores p53 nuclear
localization and sensitizes cancer cells to DNA damage, PNAS vol
105, no. 44, pages 16985-16963, 2008.
April 12:
Session 18 Treatment tactics: Chemotherapy cont.
Goals: Students will learn about the biochemistry of action of cancerspecific chemotherapies and compare and contrast them to more broadbased cytotoxic drugs.
Reading: http://www.nature.com/nm/journal/v17/n3/full/nm0311283.html: Targeting the missing links for cancer therapy. Nature
Medicine 17, 283-284, 2011.
April 17:
Session 19* Treatment tactics: Harnessing the Immune system
Goals: students will learn about new approaches to activate the immune
system to destroy cancers.
*Tues., Journal Club Paper discussion: 6th group student leaders
http://www.nature.com/nm/journal/v17/n7/full/nm.2390.html
Broad antigenic coverage induced by vaccination with virus-based
cDNA libraries cures established tumors. Nature Medicine, 17,
854-859, 2011.
Readings: http://www.nature.com/nm/journal/v17/n3/full/nm0311296.html: Timeline: a decade of advances in immunotherapy.
Nature Medicine 17, 296, 2011.
April 19:
Session 20 Treatment tactics: Harnessing the Immune system cont. and
Student Group 1 presentation
Goals: Abbreviated lecture on immune-based cancer treatment
Group 1 presentation
April 24:
Session 21 Tactics for prevention: Avoiding carcinogens and Student
Student Group 2 presentation
Goals: Abbreviated lecture on the biological basis for the success of
avoiding carcinogens (smoke, sun, chemical….) in the prevention of
cancer.
Reading: Cancer: Beg. Guide-Chapter 13
Group 2 presentation
April 26:
Sessions 22 Tactics for prevention: Avoiding carcinogens cont. and
Student Group 3 presentation
Goals: Abbreviated lecture #2 on the biological basis for the success of
avoiding carcinogens (smoke, sun, chemical….) in the prevention of
cancer.
Group 3 presentation
May 1:
Session 23 Tactics for prevention: Lifestyle changes
Goals: Students will learn the basic biology of the recommendations for
suggested dietary and life style changes that are purported to reduce the
likelihood of cancer development
*Journal Club Paper discussion: 7th group student leaders
http://pubs.acs.org/doi/full/10.1021/jm101199t
Selective Depletion of Mutant p53 by Cancer Chemopreventive
Isothiocyanates and Their Structure−Activity Relationships.
Journal of Medicinal Chemistry 2011 54 (3), 809-816
Reading: Cancer Cell Metabolism and Cancer Treatment, Aurel
Lupulescu. Australia: Harwood Academic Publishers, 2010. ISBN
905702604X. Chap. 7, pgs, 173-208.
May 3:
Session 24Quiz and Latest findings and research
Goals: This last lecture and discussion will be devoted to newly published
cancer research findings.
*Paper discussion: Research article to be determined based on latest
findings.
May 8:
Session 26 Summary and Student Group 4 presentation
Goals: Semester Summary and
Group 4 presentation