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MICa 8013

MICa 8013, TRANSLATIONAL CANCER RESEARCH

(2 Credits; Prerequisites MICa 8012, MICa 8004 or instructor’s consent)

Spring 2016, Tuesdays, 8:00-8:50AM, 2-118 Moos Tower

Course Coordinators:

David Potter, M.D., Ph.D., 625-8933, dapotter@umn.edu

David Largaespada, Ph.D., 3-129 CCRB, 626-4979, larga002@umn.edu

Course Description:

Summary:
The goals of the course are to expose Ph.D. students to clinical issues in cancer research and to discuss translational research projects as they pertain to a variety of cancers.  In particular, we will present cutting-edge concepts in cancer treatment including immunotherapy, anti-angiogenesis, small molecules, pharmacogenomics, and cancer prevention in high-risk populations.  We will emphasize exciting and controversial topics in treatment of a variety of important cancers.

Topics/ Participants:

  • Introduction – Dr. David Potter
  • Pathology – Dr. Michael Linden
  • Biostatistical Methods – Dr. John Connett
  • History of Radiation Oncology– Dr. Jianling Yuan
  • Experimental Therapeutics – Dr. David Potter
  • Sequencing – Dr. Scott Dehm
  • Leukemia – Dr. Jeffrey Miller
  • Vascular Complications – Dr. Anne Blaes
  • Prostate Cancer – Dr. Christopher Warlick
  • Lung Cancer – Dr. Robert Kratzke
  • Pediatric Cancer – Dr. Brenda Weigel
  • Epigenetic Therapy for Cancer – Dr. David Largaespada
  • Breast Cancer – Dr. Douglas Yee
  • Immunotherapy for Cancer – Dr. Chris Pennell


Who this course is designed for:

Students will be 2nd year Cancer Biology track students in the MICaB PhD program, but is open to other students who can register with instructor approval.  Postdoctoral fellows may want to audit this course. They must have completed and passed a basic cancer biology graduate course (MICa 8004) before registering for this class.  They should be knowledgeable about cancer biology, but may have little, if any, clinical knowledge.

Student Performance Objectives:
After completing this course we expect students to understand the basic kinds of cancer therapy, stages of translational research from pre-clinical studies through Phase I/II/III trials, and be able to read and understand current literature in these areas.  In addition, students should develop the skills to critically evaluate translational cancer research data and new ideas and do so in a class room/discussion setting.  Finally, they should be capable of developing independent ideas and presenting them clearly in oral presentations.

Clinical Experience:
As part of this course students will have an opportunity to experience out of class clinical experiences by attendance at their choice of a tumor board during the semester.  They should attend their choice weekly during the semester.

Text and Reference Materials:
No text is assigned.  Lecturers will provide pertinent reading materials (usually a published peer-reviewed manuscript) at least 2 days before their first lecture. Course materials will be made available to you on the Moodle course site.

HIPAA training

All participants in this course must complete University required HIPPA training before the class starts.  This can be found at: http://www.ahc.umn.edu/privacy/privtraining/home.html

Grading:

  • One take-home exam – 50%
  • In class paper presentation – 25%
  • Clinical experience/participation – 25%


Please show up to class on time! We only have 50 minutes. There will be 1 take home problem set, worth 50% of the final grade.  The take home exam will consist of a paper to read and 3-5 questions related to the paper.  We expect a 3-5 page written answer to these questions – possibly with illustration(s) to help explain your points.  Please email your take home exam answers to Dr. Largaespada AND turn in a printed copy.

25% of the grade will be based on an in class presentation describing a breakthrough in cancer treatment including significant clinical research. Students can use PowerPoint and data projector or overhead transparencies. Topics should be approved with Dr. Potter or Dr. Largaespada prior to the presentations at the end of the semester.

Participation and clinical experiences will make up the final 25% of the grade. Students will be required to spend time in clinical “experiences” in the form of weekly attendance at a clinical board meeting.  These are held at different times and places during each week.  For this experience, all participants in this course must complete University required HIPPA training before the class starts. 
This can be found at: http://www.privacysecurity.umn.edu/training/home.html

See the schedule below:

  • Thoracic Oncology Tumor Board: Dr. Robert Kratzke, Dr. Rafael Andrade.  Tuesdays at noon. Lillehei Conference room (first floor of the DVRCC/Masonic Cancer Center building). Schedule subject to change – please contact director with questions.
  • Breast Cancer Tumor Board: Dr. Doug Yee, Dr. Todd Tuttle.  Fridays at 7 AM. Mayo Building C456. Schedule subject to change, please contact Susan Pappas-Varco to receive email schedule announcements. (spappas-varco@umphysicians.umn.edu)
  • Peds HemOnc Conferences:  Dr. Brenda Weigel.  Wednesdays at 8:00am in Amplatz 4th Fl Wards Conf Room.
  • Head and Neck Tumor Board:  Dr. Bevan Yueh, Dr. Frank Ondrey. Fridays at 11 AM in PWB 8335. Schedule subject to change – please contact director with questions.
  • Neuro-oncology Tumor Board:  Dr. Matthew Hunt. Mondays at 1 PM in Mayo C456 Schedule subject to change – please contact director with questions.
  • Hematology/Oncology Tumor Board:  Dr. Robert Kratzke.  Wednesdays at noon (No meeting the 1st Wednesday of the month). Pediatric conference room on the 13th floor bridge between PWB and Moos Tower. Schedule subject to change – please contact director with questions.
  • Hematological Malignancy Conference: Dr. Bruce Peterson. 2nd and 4th Monday at 4:15pm in D175 Mayo. Schedule subject to change – please contact director with questions.

 

Syllabus:

1-19    INTRO:  Introduction; Background; Description of in class presentation, take home exam, and clinical experience.

            LECT 1: History of Chemotherapy

Dr. David Potter

Paper(s) for Dr. Potter’s Lecture:
Einhorn LH and Donohue J. 1977. Cis-Diamminedichloroplatinum, Vinblastine, and Bleomycin Combination Chemotherapy in Disseminated Testicular Cancer. Annals of Internal Medicine. 87: 293-298.

Romond EH, et al. 2005. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. Oct 20;353(16):1673-84.

1-26    LECT 2: Pathology

Dr. Michael Linden

Paper(s) for Dr. Linden’s Lecture:
Van Den Tweel, J. and Taylor, CR. A brief history of pathology. Virchows Arch (2010). 457:3-
10. DOI 10.1007/s00428-010-0934-4

Haarburger, D. and Pillay, TS. Historical perspectives in diagnostic clinical pathology:
development of the pregnancy test. J Clin Pathol. 2011, V.64;6:546-548.

Pathology Training PDF: http://www.pathologytraining.org/career/documents/PathologyCareers.pdf

2-2      LECT 3: Survival Analysis, Surrogate Endpoints, Ethical Issues and FDA Issues
            Dr. John Connett

            Paper(s) for Dr. Connett’s Lecture:
Case 13 in Data Monitoring in Clinical Trials – A Case Studies Approach, by D. DeMets, C. Furberg, and Lawrence Friedman (Springer, 2006).

Chimowitz et al., “Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis” (2011), NEJM 365: 993-1003.

Broderick J (Editorial) “The Challenges of Intracranial Revascularization for Stroke Prevention” (2011) NEJM 365: 1054-1055.

Kolata G: “Study is Ended as a Stent Fails to Stop Strokes” NYTimes Sept 7, 2011;
    http://www.nytimes.com/2011/09/08/health/research/08stent.html...

               

2-9    LECT 4: Brief Overview of Radiobiology & Clinical Radiotherapy
Dr Jianling Yuan

Paper(s) for Dr. Yuan’s Lecture:
Begg, AC, Haustermans, K., et al. The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis. Radiotherapy and Oncology 50 (1999). 13-23.

Fleckenstein, K., Gauter-Fleckenstein, B., et al. Using Biological Markers to
Predict Risk of Radiation Injury. Seminars in Radiation Oncology. 2007. 17:89-98.

2-16    LECT 5: Experimental Therapeutics/Phase I trials
Dr. David Potter

Paper(s) for Dr. Potter’s Lecture:

Ethics of phase 1 oncology studies: reexamining the arguments and data.
Agrawal M, Emanuel EJ. JAMA. 2003 Aug 27;290(8):1075-82.

Short preoperative treatment with erlotinib inhibits tumor cell proliferation in hormone receptor-positive breast cancers. Guix M, Granja Nde M, Meszoely I, Adkins TB, Wieman BM, Frierson KE, Sanchez V, Sanders ME, Grau AM, Mayer IA, Pestano G, Shyr Y, Muthuswamy S, Calvo B, Krontiras H, Krop IE, Kelley MC, Arteaga CL. J Clin Oncol. 2008 Feb 20;26(6):897-906. doi: 10.1200/JCO.2007.13.5939. Epub 2008 Jan 7.

2-23    LECT 6: Cancer Genomics in Clinical Trial Design
            Dr. Scott Dehm

            Background Reading for Lecture:
            Iyer G et al.  Genome Sequencing Identifies a Basis for Everolimus Sensitivity.  Science.  338:221, 2012.

            Roychowdhury S et al.  Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study.  Science Translational Medicine.  3:1-10, 2011.

            Assigned Paper for Lecture:
            Wu Y-M et al.  Identification of Targetable FGFR Gene Fusions in Diverse Cancers.  Cancer Discovery.  3:636-647, 2013.

3-1      LECT 7: NK and their receptors in cancer and transplantation.
Dr. Jeffrey Miller

Paper(s) for Dr. Jeffrey Miller’s Lecture:

Miller JS, et al. 2005. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. Apr 15;105(8):3051-7. Epub 2005 Jan 4. 

Cooley S, Weisdorf DJ, Guethlein LA, Klein JP, Wang T, Le CT, Marsh SG, Geraghty D, Spellman S, Haagenson MD, Ladner M, Trachtenberg E, Parham P, Miller JS. (2010). Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood. 116(14):2411-9.

Andres Wiernik, Bree Foley, Bin Zhang, et al., Targeting Natural Killer Cells to Acute Myeloid Leukemia In Vitro with a CD16x22 Bispecific Killer Cell Engager and ADAM17 Inhibition. Clin Cancer Res 2013;19:3844-3855. Published OnlineFirst May 20, 2013.

Rizwan Romee,1 Bree Foley,1 Todd Lenvik,1 Yue Wang,2 Bin Zhang,1 Dave Ankarlo,1 Xianghua Luo,3 Sarah Cooley,1 Mike Verneris,4 Bruce Walcheck,2 and Jeffrey Miller1, NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17), Blood 2013.

Michelle K. Gleason, Michael R. Verneris, Deborah A. Todhunter, et al. Bispecific and Trispecific Killer Cell Engagers Directly Activate and Cytokine Production Human NK Cells through CD16 Signaling and Induce Cytotoxicity. Mol Cancer Ther 2012;11:2674-2684. Published OnlineFirst October 17, 2012.

3-8      LECT 8: Pediatric Cancer
Dr. Brenda Weigel

Paper(s) for Dr. Weigel’s Lecture:
Bostrom BC, et al. 2003. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. May 15;101(10):3809-17. Epub 2003 Jan 16.

 
TAKE HOME EXAM ASSIGNED

 

3-15    Spring Break – NO CLASS

3-22    LECT 9: Prostate Cancer Biomarkers
Dr. Christopher Warlick

Paper(s) for Dr. Warlick’s Lecture:
Huggins C and Hodges CV. 2002. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate. Journal of Urology. Vol. 168, 9-12. (Reprint permission from Cancer Res, 1:293-297, 1941.)

Andriole et al. (2009). Mortality Results from a Randomized Prostate-Cancer Screening Trial. N Engl J Med, 360:1310-1319.

Schroder et al. (2009). Screening and Prostate-Cancer Mortality in a Randomized European Study. N Engl J Med, 360:1320-1328

3-29    LECT 10 Lung Cancer: Genetics and Beyond
Dr. Robert Kratzke, M.D.

Paper(s) for Dr. Kratzke’s Lecture:
Paez JG, et al. 2004. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. Jun 4;304(5676):1497-500.

Ding L, et al. 2008. Somatic mutations affect key pathways in lung adenocarcinoma. Nature.  455(7216):1069-75.

Weir BA, et al. 2007. Characterizing the cancer genome in lung adenocarcinoma. Nature. 450(7171):893-8.

TAKE HOME EXAM DUE

4-5 LECT 11: How Do We Make Advances in Breast Cancer Therapy?
Dr. Douglas Yee, M.D.

Paper(s) for Dr. Yee’s Lecture:
TBD

4-12    LECT 12: Epigenetic Therapy for Cancer

Dr. David Largaespada

Paper(s) for Dr. Largaespada’s Lecture:
            TBD

4-19    LECT 13:  Vascular Complications of Cancer Therapy
            Dr. Anne Blaes

            Paper(s) for Dr. Blaes’ Lecture:
        Blaes AH. (2010). Cardiac Complications from Cancer Therapy. Minnesota Medicine.
               93(10):40-4. PMID: 21140761

                Mulrooney DA, Yeazel MW, et al. (2009). Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. 339:b4606. PMID: 19996459

4-26    LECT 14: Immunotherapy for Cancer

Dr. Chris Pennell

Paper(s) for Dr. Pennell’s Lecture: 
Porter DL, et al. 2015. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Immunotherapy. Sept 2; 7(303):303ra139.

Rizvi NA, et al. 2015. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. Mar 16;16(3):257-65. Epub 2015 Feb 20.

5-3      Student Presentations

5-10    FINALS WEEK – Student Presentations (Tuesday at 10:30am)