| WEEK # | TOPICS | READINGS |
|---|---|---|
| 1 |
Introduction | No Readings |
| 2 |
Of tumor suppressors and oncogenes |
Schwab, M., J. Ellison, et al. "Enhanced Expression of the Human Gene N–myc Consequent to Amplification of DNA may Contribute to Malignant Progression of Neuroblastoma." Proceedings of the National Academy of Sciences 81, no. 15 (1984): 4940–44. Baker, S. J., S. Markowitz, et al. "Suppression of Human Colorectal Carcinoma Cell Growth by Wild–type p53." Science 249, no. 4971 (1990): 912–15. |
| 3 |
Cancer stem cells and minimal residual disease |
Lapidot, T., C. Sirard, et al. "A Cell Initiating Human Acute Myeloid Leukaemia after Transplantation into SCID Mice." Nature 367, no. 6464 (1994): 645–48. Gerber, J. M., B. D. Smith, et al. "A Clinically Relevant Population of Leukemic CD34+CD38– Cells in Acute Myeloid Leukemia." Blood 119, no. 15 (2012): 3571–77. |
| 4 |
Can we model human cancers in mice? |
Harris, A. W., C. A. Pinkert, et al. "The E Mu–myc Transgenic Mouse. A Model for High–incidence Spontaneous Lymphoma and Leukemia of Early B Cells." The Journal of Experimental Medicine 167, no. 2 (1988): 353–71. Ishikawa, F., S. Yoshida, et al. "Chemotherapy–resistant Human AML Stem Cells Home to and Engraft within the Bone–marrow Endosteal Region." Nature Biotechnology 25, no. 11 (2007): 1315–21. |
| 5 |
Making a better Mouse Man—Recent developments in humanized mouse technologies |
Shultz, Leonard D., Yoriko Saito, et al. "Generation of Functional Human T–cell Subsets with HLA–restricted Immune Responses in HLA Class I Expressing NOD/SCID/IL2rγnull Humanized Mice." Proceedings of the National Academy of Sciences 107, no. 29 (2010): 13022–27. Lan, P., N. Tonomura, et al. "Reconstitution of a Functional Human Immune System in Immunodeficient Mice through Combined Human Fetal Thymus / Liver and CD34+ Cell Transplantation." Blood 108, no. 2 (2006): 487–92. |
| 6 |
Sophisticated models of de novo human tumors in humanized mice |
Moriya, K., M. Suzuki, et al. "Development of a Multi–step Leukemogenesis Model of MLL–rearranged Leukemia using Humanized Mice." PLoS One 7, no. 6 (2012): e37892. Washburn, M. L., M. T. Bility, et al. "A Humanized Mouse Model to Study Hepatitis C Virus Infection, Immune Response, and Liver Disease." Gastroenterology 140, no. 4 (2011): 1334–44. |
| 7 |
Visit to Chen Research Lab | No Readings |
| 8 |
The immune system and cancer—Cancer Immunoediting hypothesis |
Shankaran, V., H. Ikeda, et al. "IFN gamma and Lymphocytes Prevent Primary Tumour Development and Shape Tumour Immunogenicity." Nature 410, no. 6832 (2001): 1107–11. Muul, L. M., P. J., Spiess, et al. "Identification of Specific Cytolytic Immune Responses against Autologous Tumor in Humans Bearing Malignant Melanoma." Journal of Immunology 138, no. 3 (1987): 989–95. |
| 9 |
T cell mediated immunotherapy |
Attia, P., G. Q. Phan, et al. "Autoimmunity Correlates with Tumor Regression in Patients with Metastatic Melanoma Treated with Anti–cytotoxic T–Lymphocyte Antigen–4." Journal of Clnical Oncology 23, no. 25 (2005): 6043–53. Vudattu, N. K., F. Waldron–Lynch, et al. "Humanized Mice as a Model for Aberrant Responses in Human T Cell Immunotherapy." Journal of Immunology 193, no. 2 (2014): 587–96. |
| 10 |
Improving combination chemotherapy and immune–based therapies based on lessons learned from humanized mice |
Rambaldi, A., M. Lazzari, et al. "Monitoring of Minimal Residual Disease after CHOP and Rituximab in Previously Untreated Patients with Follicular Lymphoma." Blood 99, no. 3 (2002): 856–62. Pallasch, C. P., I. Leskov, et al. "Sensitizing Protective Tumor Microenvironments to Antibody–mediated Therapy." Cell 156, no. 3 (2014): 590–602. |
| 11 |
Personalized mice—Part 1: Mouse Avatars |
Villarroel, M. C., N. V. Rajeshkumar, et al. "Personalizing Cancer Treatment in the Age of Global Genomic Analyses: PALB2 Gene Mutations and the Response to DNA Damaging Agents in Pancreatic Cancer." Molecular Cancer Therapeutics 10, no. 1 (2011): 3–8. Garralda, E., K. Paz, et al. "Integrated Next–generation Sequencing and Avatar Mouse Models for Personalized Cancer Treatment." Clinical Cancer Research 20, no. 9 (2014): 2476–84. |
| 12 |
Personalized mice—Part 2: Co–clinical trials |
Chen, Z., K. Cheng, et al. "A Murine Lung Cancer Co–clinical Trial Identifies Genetic Modifiers of Therapeutic Response." Nature 483, no. 7391 (2012): 613–17. Chen, Z., E. Akbay, et al. "Co–clinical Trials Demonstrate Superiority of Crizotinib to Chemotherapy in ALK–rearranged Non–small Cell Lung Cancer and Predict Strategies to Overcome Resistance." Clinical Cancer Research 20, no. 5 (2014): 1204–11. |
| 13 |
Class presentation and course evaluation | No Readings |