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MICa 8004 - Biology of Cancer

Biology of Cancer – MICA 8004
Spring Semester, 2015
M,W,Th,F, 9:05-9:55am, 2-580 MoosTower

David Largaespada (Course Director), 6-4979,, 3-129 CCRB
Jaime Modiano (Course Co-Director), 5-7436,, 410 VMC
Anindya Bagchi (

Martina Bazzaro (

Scott Dehm (
Timothy Hallstrom (
Ameeta Kelekar (

Carol Lange (
Katie Leehy ( 

Louis Mansky (
Deepali Sachdev (
Kaylee Schwertfeger ( 

Timothy Starr (
Douglas Yee (

The Biology of Cancer, 2nd Edition. Robert A. Weinberg, Garland Publishing, New York, 2008.

Course Format
The course will be divided into 15 blocks consisting of 4 meetings per block. Within each block, the first two meetings will be lectures with assigned textbook chapters and/or journal articles. These lectures will cover key concepts that you will be expected to know for the final exam. Students should expect to spend time outside of class to learn techniques relevant to the assigned reading material. Course materials will be available thru a Moodle course site.

The third meeting will be a journal club-style discussion of a paper that is related to the topic of the block. Students are expected to read the entire assigned paper before class and be ready to discuss it in detail. Students will be separated into groups and each group will be expected to present part of the paper to the class. The section your group will present will not be assigned until the day of class that you present, therefore, be prepared to discuss any part of the paper. You will have 10 minutes with your group at the beginning of class to prepare your presentation. Presentations will be approximately 5 minutes long. These assigned groups will change three times during the course. Your group assignments will be handed out the first day of class.

The instructor will e-mail a problem-solving quiz to each student shortly after the third meeting. Students will e-mail their answers back to the instructor before the beginning of the fourth meeting, after which the instructor will present acceptable answers and lead a discussion of alternative answers and their weaknesses. The instructor will also summarize the Key Concepts of the block at the fourth meeting.

The exams will include 15 problem-solving quizzes, one per block, and a fact-based short answer format final exam. The quiz may be one essay question or multiple questions. The quizzes will be e-mailed as MS Word documents by the block instructor to the students shortly after the third meeting of each block. The completed quizzes must be e-mailed by the students back to the block instructor by the beginning of the fourth meeting. Answers must be limited to 1 page, 12pt Times New Roman font, 1-inch margins, single spacing. Answers longer than 1 page will be given a score of 0. Any material available in the scientific literature may be used to answer the questions. However, students are expected to answer their own quiz independently. None of the quiz questions may be discussed with other members of the class until after the quiz. According to criteria discussed during the fourth session, the instructor will grade each quiz, and the graded quiz will be returned to students via e-mail.

The final exam will be 1 hour in length, closed book, short answer format, and focused on the Key Concepts from each block.

Course Points
Exams - 10 points will be given for each take home quiz for a total of 150 points and 75 points will be given for the final exam.

Attendance - 5 points will be given for participation during each block for a total of 75 points. Attendance points will be based on attending all classes in each block. Attendance of all meetings is expected, with an exception for one excused absence during the course (NOT one excused absence per block). Excused absences MUST be for legitimate reasons and are to be requested from the course director, David Largaespada or Jaime Modiano, when possible, before the missed meeting or immediately following.

Take Home Quizzes (15 at 10 pts each) – 150 points
Attendance Points (15 at 5 pts each block) – 75 points
Final Exam – 75 points
Total Points Available – 300

Block Topic Lecturer Group Dates (W,Th,F,M)
1 Introduction to the Course/Cancer Pathology/The TCGA ModianoStarr A Groups Jan. 21,22,23,26
2 Cancer Genetics: Cancer Viruses and Experimental Genetics Mansky A Groups Jan. 28, 29,30, Feb 2
3 Cell Signaling I: The cytoplasm (GF receptors, G-protein coupled receptors) Lange A Groups Feb. 4,5,6,9
4 Cell Signaling II: RAS, SRC, P13K, SHH, WNT, TGF Leehy A Groups Feb 11,12,13,16
5 Cell Signaling III:  The nucleus (steroid hormone receptors, Fos/Jun, JAK-STAT) beta Dehm A Groups Feb 18,19,20,23
6 Tumor suppressor genes; Genome Instability Bagchi B Groups Feb. 25,26,27, March 2
7 RB/ Cell Cycle/P53 Hallstrom B Groups March 4,5,6,9
8/9 Apoptosis
Kelekar B Groups March 11,12,13,23,25,26
10 Cellular Immortalization; Cancer Stem Cells Largaespada B Groups April 1,2,3,6
11 Angiogenesis Bazzaro C Groups April 8,9,10,13
12 Invasion & Metastasis Schwertfeger C Groups April 15,16,17,20
13 Cancer Therapy I: Small molecules and Targeted Therapy Sachdev/Yee C Groups April 22,23,24,27
14 Human Cancer and Microbes: Bacteria and Viruses Largaespada C Groups April 29l 30, May 1,4
15 Cancer Therapy II: Tumor Immunology & Immune Therapies Modiano C Groups May 6,7,8,


Spring break March 16-20

MICA 8004 Reading List - Spring Semester 2015

Please read the material listed for each date BEFORE coming to class.

Block 1: Introduction to the Course/Cancer Pathology/The TCGA

Jan. 22nd - 1) Skim the first chapter of the textbook (Weinberg, Ch 1, pp. 1-29). Use the bold words throughout the chapter to judge whether or not you already have this knowledge.  If you can read the bold words and could define them in an essay question on a test, then you don't need to read the chapter thoroughly. Watch at least one of the movies on the CD that comes with the books. This chapter is a review of the fundamentals of genetics. You should already know most of what is in this chapter.

2) Go to The Cancer Genome Atlas homepage ( Attempt to download all the somatic mutations that have been found in the colon adenocarcinoma samples analyzed by the TCGA.  Hint: Use the data matrix.  The downloaded file will be a zip file ~50 Mb (i.e. I wouldn't try this at home if you have a slow connection).  Once you unzip the file, see if you can find the first mutation listed. Hint: the file will have the extension .maf and you should open it using a basic text editor.

Jan. 23rd - 1) Start by reading the Synopsis and prospects and Key concepts (pp. 66-69) in Weinberg, Chapter 2. If some of the key concepts are new to you, read that portion of the chapter. Spend some time on the first part of the chapter learning nomenclature used to describe cancer pathology.
2) Read Hanahan, D. and Weinberg, R.A. Hallmarks of Cancer: The Next Generation. 2011. Cell 144,

Jan. 24th - Journal article: Be prepared to present every figure and table. Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression. Takeda, et al., Nature Genetics, 2015 Advance Online Publication. (Hot off the press, as they say).

Jan. 27th – (additional readings, not required)

A good historical account of cancer research: "The Emperor of All Maladies: A Biography of Cancer" by Siddhartha Mukherjee. This is a 1,000 page epic, but it is good for skimming.

Block 2: Cancer Genetics: Cancer Viruses and Experimental Genetics

Jan. 28th -  Weinberg Chapter 3, read the Synopsis, Prospects, & Key Concepts pp. 86-90. Skim the
chapter and read the bolded words/terms. If you understand key concepts and bolded word/terms, no further reading required.

Temin HM and H Rubin. 1958. Characteristics of an assay for Rous sarcoma virus and Rous sarcoma cells in tissue culture. Virology 6:669-688.

Jan. 29th - Weinberg Chapter 4, read the Synopsis, Prospects, & Key Concepts pp. 112-116. Skim the
chapter and read the bolded words/terms. If you understand key concepts and bolded word/terms, no further reading required.

Jan. 30th  - Stehelin D, HE Varmus, JM Bishop, PK Vogt. 1976.  DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA.  Nature 260:170-173.

Feb. 1st – (additional readings, not required)

Read "The Emperor of All Maladies: A Biography of Cancer" by Siddhartha Mukherjee.


Block 3: Cell Signaling I: The Cytoplasm (GF Receptors, G-Protein Coupled Receptors)

*Please use the textbook as a general point of reference for background to signaling. Topics of interest include mechanisms of growth factor tyrosine kinase receptor (EGFR family members) signaling and regulation of downstream protein kinase cascades (MAPKs and PI3K/Akt). The context for this section is the role of dysregulation of these regulatory molecules in cancer biology.

Feb 4 – Weinberg Chapter 5* – Kinases and Kinase Receptors (integrin receptors will be covered

            Feb 5 – Weinberg Chapter 5 cont.* – Passing the signal: Ras and Downstream Signaling to MAP Kinase Cascades

Required reading (short review):
Ferrell JE Jr. What do scaffold proteins really do? Sci STKE. 2000 Oct 3;2000 (52):PE1. Review.

Feb 6 - Signaling specificity (downstream of Ras) in cancer biology - Discuss Gupta et al Research Article paper in class.

Required reading
AR Ramjaun and J Downward. Ras and Phosphoinositide 3-Kinase: Partners in Development and Tumorigenesis. Cell Cycle 6:23, 2902-2905, 2007 (this is a good preparation for the research article below)

S Gupta et. al (Julian Downward lab). Binding of Ras to PI3K p110a is required for Ras-driven tumorigenesis in mice. Cell 129: 957-968, 2007.

Feb 9 – Review / Discussion of Key Concepts

Required reading
Cox AD1, Fesik SW2, Kimmelman AC3, Luo J4, Der CJ. Drugging the undruggable RAS: Mission possible? Nat Rev Drug Discov. 2014 Nov;13 (11):828-51. doi: 10.1038/nrd4389. Epub 2014 Oct 17. (therapies)

Block 3 Additional Reading (highly suggested):

Dittrich A1, Gautrey H, Browell D, Tyson-Capper A. The HER2 Signaling Network in Breast Cancer-Like a Spider in its Web. J Mammary Gland Biol Neoplasia. 2014 Dec 28. [Epub ahead of print]  (signaling complexity/specificity)

Gentry L, Samatar AA, Der CJ. Inhibitors of the ERK mitogen-activated protein kinase cascade for targeting RAS mutant cancers. Enzymes. 2013;34 Pt. B:67-106. doi: 10.1016/B978-0-12-420146-0.00004-4. Epub 2013 Nov 7. Review. (therapies including comprehensive listing of drugs)

Block 4: Cell Signaling II: RAS, SRC, P13K, SHH, WNT, TGFbeta

Feb. 11th - Weinberg Chapter 6, pgs. 175-202

Feb. 12th - Weinberg Chapter 6, pgs. 206-228

Feb. 13th - Yan Wang,Qingqing Ding,Chia-Jui Yen, et. al. The Crosstalk of mTOR/S6K1 and
Hedgehog Pathways. Cancer Cell, Volume 21, Issue 3, 374-387, 20 March 2012

Feb. 16th – (additional readings, not required)

Cancer Cell. 2012 Nov 13;22(5):571-84. doi: 10.1016/j.ccr.2012.08.013. Dependency of
Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation.Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Céspedes MV, Sevillano M, Nadal C, Jung P, Zhang XH, Byrom D, Riera A, Rossell D,Mangues R, Massagué J, Sancho E, Batlle E.

Cancer Cell. 2012 Nov 13;22(5):668-82. doi: 10.1016/j.ccr.2012.10.009. Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas. Lito P, Pratilas CA, Joseph EW, Tadi M, Halilovic E, Zubrowski M, Huang A, Wong WL, Callahan MK, Merghoub T, Wolchok JD, de Stanchina E,Chandarlapaty S, Poulikakos PI, Fagin JA, Rosen N.

Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Muranen T, Selfors LM, Worster DT, Iwanicki MP, Song L, Morales FC, Gao S, Mills GB,Brugge JS. Cancer Cell. 2012 Feb 14;21(2):227-39.

Block 5: Cell Signaling III: The Nucleus (Steroid Hormone Receptors, Fos/Jun, JAK-STAT)

Feb. 18th - Weinberg Chapter 1.6, 1.7, 1.8, and Weinberg Chapter 6.1, 6.5, 6.6, 6.8, 6.10, 6.12 (these
should already have been read in preparation for previous Blocks)

Chi P, Allis DC, Wang GG.  Covalent histone modifications—miswritten, misinterpreted and mis-erased in human cancers.  Nature Reviews Cancer 10:457-469, 2010.

Feb. 19th - Jozwik KM, Carroll JS.  Pioneer factors in hormone-dependent cancers.  Nature Reviews
Cancer.  12:381-385, 2012.

Feb. 20th - Hurtado A, Holmes KA, Ross-Innes CS, Schmidt D, Carroll JS.  FOXA1 is a key
determinant of estrogen receptor function and endocrine response.  Nature Genetics  43:27-33, 2011.

Feb. 23rd – (additional readings, not required)

Cheung E and Ruan Y.  Determination of transcription factor binding.  Nature Genetics 43: 11-12, 2011.

Ross-Innes CR et al., Differential oestrogen receptor binding is associated with clinical outcome in breast cancer.  Nature 481: 389-93, 2012.

Cowper-Sal L et al., Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression.  Nature Genetics  44:1191-1198, 2012. 

Block 6: Tumor Suppressor Genes, Genome Instability

Feb. 25th - Weinberg Chapter 7, pgs. 209-254

Feb. 26th - Weinberg Chapter 12, pgs. 463-526

Feb. 27th – The Landscape of Microsatellite Instability in Colorectal and Endometrial Cancer Genomes
Cell, Volume 155, Issue 4, 7 November 2013, Pages 858–868

March 2nd – (additional readings, not required)

Block 7: RB/Cell Cycle/P53

March 4th - Weinberg Chapter 8

March 5th - Weinberg Chapter 9.1-9.12

March 6th - CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.
Cancer Cell. 2014 Jul 14;26(1):136-49.

March 9th – (additional readings, not required)

Keith W. Orford1 & David T. Scadden. Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nature Reviews Genetics 9, 115-128 (February 2008) | doi:10.1038/nrg2269

Block 8/9: Apoptosis Autophagy/Metabolism

March 11 - Ola, M.S., M. Nawaz, and H. Ahsan, Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem, 2011. 351(1-2): p. 41-58

Additional Reading (optional) - Youle, R.J. and A. Strasser, The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol, 2008.9(1): p. 47-59

March 12 - Mizushima, N. and M. Komatsu, Autophagy: renovation of cells and tissues. Cell, 2011. 147(4): p. 728-741

March 13 – Review Apoptosis and Autophagy

March 23 – Cantor, J.R. and D.M. Sabatini, Cancer cell metabolism: one hallmark, many faces. Cancer Discovery 2012. 2(10): p. 881-898

Additional Reading (optional) - Leone, R.D. and R.K. Amaravadi, Autophagy: a targetable linchpin of cancer cell metabolism. Trends Endocrinol Metab, 2013.24(4): p. 209-217.

March 25 – Review Cancer Metabolism

March 26 – Xie, J.M., et al. (2014). TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer Res 74, 5127-5138.

March 27 – Back-to-back papers on mitochondrial myruvate transporter:
1. Yang, C., , et al. (2014). Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell 56, 414-424.
2. Schell, J.C., et al. (2014). A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol Cell 56, 400-413.

Additional Reading (optional) - Szlosarek, P.W., Lee, S., and Pollard, P.J. (2014). Rewiring mitochondrial pyruvate metabolism: switching off the light in cancer cells? Mol Cell 56, 343-344.

Vacanti, N.M., et al. (2014). Regulation of substrate utilization by the mitochondrial pyruvate carrier. Mol Cell 56, 425-435.

March 30  – Discussion and review of assignments

Block 10: Cellular Immortalization; Cancer Stem Cells

April 1st - Weinberg Chapter 10, pgs. 391-437

April 2nd - Weinberg Chapter 11, pgs. 439-509

April 3rd - Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, Heath S, Baty JD, Klco JM, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley TE, Link DC, Wilson RK. Nature. 2014 Dec 8. doi: 10.1038/nature13968.

April 6th – (additional readings, not required)
Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Tomasetti C, Vogelstein B. Science. 2015 Jan 2;347(6217):78-81. doi: 10.1126/science.1260825.

Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells. Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, Hein K, Vogt R, Kemler R. Science. 2012 Jun 22;336(6088):1549-54. doi: 10.1126/science.1218370.

Block 11: Angiogenesis

April 8th - Weinberg Chapter 13

April 9th – Weinberg Chapter 13

April 10th -  Rac1/Pak1/p38/MMP-2 axis regulates angiogenesis in ovarian cancer. Gonzalez-Villasana, Fuentes-Mattei, Ivan, Dalton, Rodriguez-Aguayo, Fernandez-de Thomas, Aslan, Monroig-Bosque, Velazquez-Torres, Previs, Pradeep, Kahraman, Wang, Kanlikilicer, Ozpolat, Calin, Sood, Lopez-Berestein. Clin Cancer Res. 2015 Jan 16. pii: clincanres.2279.2014. [Epub ahead of print]

April 13th – (additional readings, not required)

Block 12: Invasion and Metastasis

April 15th - Weinberg Chapter 14 pgs. 641-685

April 16th - Weinberg Chapter 14 pgs. 686-689, 695-719

April 17th - A Noncanonical Frizzled2 Pathway Regulates Epithelial-Mesenchymal Transition and Metastasis. Gujral et al., Cell 159(4), 844-856, 2014.

April 20th – (additional readings, not required)
1.  Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors
and cancer: trials and tribulations. Science 2002;295(5564):2387-92.

2. Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev
Cancer 2009;9(4):239-52.

3.Klein CA. Cancer. The metastasis cascade. Science 2008;321(5897):1785-7.

4.Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-
mesenchymal transition generates cells with properties of stem cells. Cell 2008;133(4):704-15

Block 13: Cancer Therapy I: Small Molecules and Targeted Therapy

April 22nd - Weinberg Chapter 16 pgs. 797-815
April 23rd - Weinberg Chapter 16 pgs. 815-818; 825-833; 844-860

April 24th - TBD

April 27th – (additional readings, not required)

Block 14: Human Cancer and Microbes: Bacteria and Viruses

April 29th - Weinberg Chapter 11, pgs. 488-500

April 30th – Schwabe RF and Jobin C. The microbiome and cancer. Nat Rev Cancer. 2013 Nov;13(11):800-12. doi: 10.1038/nrc3610. Epub 2013 Oct 17.

May 1st - Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008 Feb 22;319(5866):1096-100. doi: 10.1126/science.1152586. Epub 2008 Jan 17.

May 4th – (additional readings, not required)


Block 15: Cancer Therapy II: Tumor Immunology and Immune Therapies

May 6th – Weinberg Chapter 15

May 7th  - TBD

May 8th  - TBD


MICA 8004 – Biology of Cancer
Key Concepts

Block 1: Cancer Pathology and the TCGA
1. Use and understand terminology describing pathological and molecular processes in cancer development and progression
2. Enumerate and provide an overview of the hallmarks of cancer and their significance to diagnosis and therapy
3. Discuss changes in the dynamics of cancer incidence and prevalence in the past 3-5 decades (i.e.,
answer the question, “is there a cancer epidemic?”)
4. Describe the histological origins of cancer and their relationship to processes of developmental biology

Block 2: Cancer Genetics: Cancer Viruses, Experimental Genetics
1. The discovery of oncogenes
2. Mechanisms that create oncogenes
3. Genetically engineered mouse models: A) Transgenic mice and B) Knock-out/Knock-in mice
4. The tumor genome – capabilities and limitations

Block 3: Cell Signaling I: The Cytoplasm (GF Receptors, G-Protein Coupled Receptors)

  1. Define what is meant by signal transduction.
  2. Be able to name/explain the function of the key components of signaling pathways and their conserved motifs that allow for protein-protein interaction and signal propagation.
  3. Understand the role of signal transduction with regard to gene expression.
  4. Be able to discuss mechanisms of signaling specificity (i.e. complexity) in normal and cancer cell biology.
  5. Be able to relate these concepts (1-4) to discussions of cancer treatments that use targeted (i.e. to signaling molecules) therapies (what strategies are being employed and what are the major challenges?).

Block 4: Cell Signaling II: RAS, SRC, P13K, SHH, WNT, TGFbeta

1. Regulation of small GTPases by GEFs and GAPs
2. Assembly of signaling complexes involving SH2 and SH3 domain containing proteins
3. PI3K signaling as a master regulator of cancer development and maintenance
4. Signal pathway regulation by a destruction complex
5. The paradoxical role of TGF-beta in cancer development and progression
6.  Feedback signal pathway regulation in cancer cell signaling

Block 5: Cell Signaling III: The Nucleus (Steroid Hormone Receptors, Fos/Jun, JAK-STAT)
1. Transcription and deregulation in cancer
2. Fos/Jun, STATs and oncogenic signal transduction pathways
3. Hormone receptors and the development and progression of prostate and breast cancers.
4. Androgen and estrogen signaling pathways, “molecularly targeted therapies” and resistance

Block 6: Tumor Suppressor Genes: Genome Instability

  1. Mechanisms for loss of heterozygoisity (LOH) during tumorigenesis
  2. DNA repair mechanisms are tumor suppressive
  3. Base excision repair
  4. Mismatch repair
  5. Homologous recombination

Block 7: RB/Cell Cycle/P53

1. The cell cycle, cyclins and their catalytic CDK binding partners
2. Timing and signals of cell fate, such as growth, quiescence, apoptosis, differentiation or senescence
3. E2F transcription factors associated with promoters of genes that control cell cycle, DNA replication and mitosis. 
4. Hypophosphorylated pRb and hyperphosphorylated pRb 
5. Loss of pRb function
6. Inactive pRb and activation of pro-apoptotic or senescence programs.

Block 8/9: Apoptosis /Autophagy/Metabolism
1. Programmed Cell Death and Apoptotic pathways in normal cells and their aberrant regulation in cancer, with special emphasis on the involvement of the Bcl-2 family of proteins
2. Autophagy as a Stress Response in normal cells, and the contradictory and contextual roles for deregulated Autophagy in tumor suppression and tumor progression
3. The Warburg Hypothesis and Metabolic Reprogramming in actively proliferating normal cells and cancer cells 
4. Apoptosis, Autophagy and Metabolism are closely linked – understanding the crosstalk, the overlap and the shared regulators

Block 10: Cellular Immortalization; Cancer Stem Cells

  1. Telomeres, the end replication problem, and immortalization
  2. Mortality limits: senescence and crisis
  3. Breakage-bridge-fusion cycles and genome instability
  4. The concept of tumor target cells, as tissue stem cells, during cancer development
  5. What is a cancer stem cell?
  6. What is the likely course of mutation accumulation in most human cancer?

Block 11: Angiogenesis

1. Tumors and intercommunication between various cell types
2. The recruitment of macrophages, fibroblasts and fibroblast and their key roles during tumor-associated angiogenesis
3. The “Angiogenic switch” and tumor-associated angiogenesis as a critical determinant of tumor growth.
4. Neo-angiogenesis as target for development of novel anticancer agents as angiogenesis inhibitors are designed to “cut off cancer’s supplies”

Block 12: Invasion and Metastasis
1. Metastatic cascade steps including 1) local invasion, 2) intravastion, 3) transport, 4) extravasation, 5) formation of micrometastases and 6) colonization
2. The process of epithelial-mesenchymal transition (EMT), during which epithelial gene expression is lost and mesenchymal gene expression is gained, contributes to tumor cell motility and invasiveness
3. MMPs promote invasion by degrading the basement membrane and releasing growth and angiogenic factors from the extracellular matrix.
4. Metastasis involves changes in the tumor cells and contributions from stromal/host cells both within the local microenvironment and at distant sites

Block 13: Cancer Therapy I: Small Molecules and Targeted Therapy
1. Understand the role of systemic therapy in reducing breast cancer deaths.
2. Identifying prognostic factors and their roles as targets for cancer therapy.
3. Describe the role for targeted therapies and mechanism of action.
4. Resistance to targeted therapies is frequently seen and can be either de novo or acquired. Understand that targeting multiple pathways may be critical.

Block 14: Human Cancer and Microbes: Bacteria and Viruses
1. Viruses and bacteria can cause human cancer. Roughly 20% of human cancer has a viral etiology.
2. Microbes are incomplete carcinogens, often cause chronic inflammation leading to cancer.
3. Viral proteins designed to enhance replication can contribute to cancer development.
4. Criteria for establishing causation differs from Koch’s postulates

Block 15: Cancer Therapy II: Tumor Immunology and Immune Therapies
1. Describe how immune surveillance constantly eliminates nascent tumors and understand the notion that, by definition, cancer has escaped immune surveillance.
2. Enumerate the features of the immune system that make it attractive to exploit for cancer therapy: specificity, memory, and the ability of immune cells to reach every part of the body that is inaccessible to conventional therapies.
3. Discuss reasons why monoclonal antibody therapy is the immune-based approach that has had the most profound effect in cancer therapy to date.
4. Discuss why overcoming cancer-mediated immune suppression is critical for the success of cell-based immune therapies.