MICaB Course Information

MICa 8004 - Biology of Cancer

Syllabus for MICa 8004 (4 credits)
Spring Semester 2008
MWThF, 9:05-9:55 am
2-118 Moos Tower

Course Coordinator, James McCarthy
2-184 Moos Tower
625-7454
mccar001@tc.umn.edu

January 23, 24, 25, 28, 30, Largaespada Genetic Mechanisms Of Cancer

Wednesday January 23rd, Lecture 1: Nature of Cancer, Genetic Theory of Cancer

Assigned Reading:

• Weinberg Chapters 1 and 2

Thursday, January 24th, Lecture 2: How Viruses Were Used to Discover Cancer Genes

Assigned Reading

• Weinberg Chapter 3

• S.Hacein-Bey-Abina, et al. LMO2 -associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science, 302: 415-419. (2003)

• U. Dave, N.A. Jenkins, and N.G. Copeland. Gene therapy insertional mutagenesis insights. Science, 303: 333 (2004).

Friday, January 25nd, Lecture 3: Methods Used to Study Cancer - including Mouse Genetics in Cancer Research

Assigned Reading

• Weinberg Chapter 4 (pp 91-108) and 11

• Collier LS, Carlson CM, Ravimohan S, Dupuy AJ and Largaespada DA. Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse. Nature. 436:272-6. (2005)

Monday, January 28th. Lecture 4: Teleomeres, Immortality, and Chromosome Instability

Assigned Reading

• Weinberg Chapter 12

• Artandi SE, Chang S, Lee SL, Alson S, Gottlieb GJ, Chin L, DePinho RA. “Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice.” Nature. 406:641-5. 2000

Tuesday, January 30th. Lecture 5: The Human Cancer Genome Project

Assigned Reading

• Weinberg Chapter 11 (review it)

• Hanahan D and Weinberg RA. The hallmarks of cancer. Cell 100:57-70. (2000).

• Futreal et al., A census of human cancer genes. Nature Reviews Cancer 4:177-183 (2004)

• Sjoblom T, et al. The consensus coding sequences of human breast and colorectal cancers. Science. Oct 13; 314:268-74. (2006).

Plus In Class Quiz Today (10 points) and distribution of first take home exam (20 points)

31 February 1, 4, 6, 7 Bitterman/Polunovsky Tumor Suppressors And Oncogenes

1/31: Didactic session - Everything you ever wanted to know about cancer… but were afraid to ask!
– assigned reading: Weinberg: chapters 4 and 7

2/1: Tumor suppressor discovery
-assigned reading: Harris, Miller, Klein, Worst, Tachibana. Suppression of Malignancy by
Cell Fusion Nature, Vol. 223, 1969, p363.

2/4: Ras, the archtype oncogene
-assigned reading: Chin L, Tam A, Pomerantz J, Wong M, Holash J, Bardeesy N, Shen Q, O'Hagan R, Pantginis J, Zhou H, Horner JW 2nd, Cordon-Cardo C, Yancopoulos GD, DePinho RA. Essential role for oncogenic Ras in tumour maintenance. Nature. 1999 Jul 29; 400(6743):468-72.

2/6: Oncogene or tumor suppressor?
-assigned reading: Eliyahu D, Michalovitz D, Eliyahu S, Pinhasi-Kimhi O, Oren M. Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci U S A. 1989 Nov; 86 (22): 8763-7.

2/7: Translation initiation machinery as a convergence point for oncogenic signaling.
-assigned reading: Avdulov S, Li S, Michalek V, Burrichter D, Peterson M, Perlman DM, Manivel JC, Sonenberg N, Yee D, Bitterman PB, Polunovsky VA. Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells. Cancer Cell. 2004 Jun; 5(6):553-63.

Plus In Class Quiz Today (10 points) and distribution of take home exam (20 points)

8, 11, 13, 14, Skubitz Cancer Biomarker Discovery

Friday February 8th, Lecture 1: Biomarkers of Cancer: Challenges in biomarker discovery

Assigned Reading:

• Weinberg Chapter 16.1 (pps 727-732)

Recommended Reading (not required):

• Journal of Proteome Research 2005, 4, 1053-1059, "So, you want to look for biomarkers" by Joshua LaBaer.

Monday February 11th, Lecture 2: Biomarkers of Cancer: Genomic techniques for biomarker discovery

Recommended Reading (not required):

• Journal of Pathology 2001, 195:41-52, "Towards a novel classification of human malignancies based on gene expression patterns" by A.A. Alizadeh, D.T. Ross, C.M. Perou, and M. van de Rijn.

Wednesday February 13th, Lecture 3: Biomarkers of Cancer: Journal club discussion

Assigned Reading: (Journal club format with class participation)

• American Journal of Pathology, 2004, 165:397-414, "Differential gene expression in ovarian carcinoma: Identification of potential biomarkers" by K. Hibbs et al.

Thursday February 14th, Lecture 4: Biomarkers of Cancer: Proteomic techniques for biomarker discovery

Recommended Reading (not required):

• "Proteomics of breast cancer: Principles and potential clinical applications" by F. Bertucci, D. Birnbaum, and A. Goncalves, Molecular & Cellular Proteomics, 5:1772-1786, 2006.

• "Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer" Zhen Zheng, Robert C. Bast, Jr., Yinhua Yu, et al, Cancer Research 64:5882-5890, August 15, 2004.

15, 18, 20, 21, 22, Southern Cancer and Viruses

Chap 8: pp 273-278, Elements of Chap 9, Chap 11: pp 441-461

25, 27, 28, 29, March 3, Lange Signal Transduction

Weinberg: Chapter 8 & 14

5, 6, 7, 10, 12, Bardwell Transcriptional Regulation in Cancer

Weinberg: pps. 19-22, 226-232, 732-734.

Reviews:
Polycomb silencers control cell fate, development and cancer. Sparmann A, van Lohuizen M. Nat Rev Cancer. 2006 Jan;6(1):38-51.

Stem Cell Chromatin Patterns: An Instructive Mechanism for DNA Hypermethylation? Joyce E. Ohm and Stephen B. Baylin Cell Cycle 6:9, 1040-1043, 1 May 2007];

13, 14, 24, 26, 27, Kelekar Mechanisms of Cell Survival and Death

Weinberg Chapter 9- Pages 325 -356

Additional Review

Kelekar, A. Autophagy in "Cell Injury: Mechanisms, Responses and Repair" Ann. N.Y. Acad. Sc. 2006. 1066:259-271.

28, 31, April 2, 3 Huang Hormones in Prostate Cancer
TBA

4, 7, 9, 10,11 McCarthy Tumor Stem Cells/ Microenvironment

Chapter 14 (April 2,4,5)

Chapter April 6,9 Chapter 12 (463-473 on stem cells)

14, 16, 17,18 Schwertfeger Inflammation and Cancer

Weinberg: Chapter 11 pp.441-452

Coussens, L. and Werb, Z. Inflammation and Cancer. Nature, 420: 860-867 (2002).

Condeelis, J. and Pollard, J.W. Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis. Cell, 124: 263-266 (2006).

21, 23, 24, 25, LeBien Hematologic Malignanices

Readings in Weinberg, from the index under the terms "chromosomal translocation" and "chronic myelogenous leukemia".

Reviews:

1) Pui C et al. Acute lymphoblastic leukemia. N Eng J Med, 350:1535, 2004

2) Ren R. Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia. Nature Rev Cancer, 5:172, 2005.

28, 30, May 1, 2, Pennell Immune Therapy

April 28 - Cancer Immunosurveillance
Bui, J.D. and Schreiber. R.D. 2007. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Current Opinion in Immunology 19:203–208

April 30 - Anti-tumor immunity
Weinberg: Chapter 15 (if students have a background in immunology, skip sections 15.1-15.6 and begin with section 15.7 on p 669).

May 1 – Humoral anti-tumor immunity Journal club
Article forthcoming

May 2 - Cellular anti-tumor immunity Journal club
Article forthcoming

5, 7, 8, 9 Yee/Sachdev Emerging Cancer Therapies

Weinberg: Chapter 16 pp. 725-737; 748-75;765-769