Allen Gown, MD
PhenoPath Laboratories
Seattle, WA

The focus of this course will be on how targeted therapies of cancer are impacting on the practice of surgical pathology. Each talk will provide an overview of the biology behind the specific targeted therapies, the indications for their use, their clinical impact, the eligibility criteria (as defined by histology, or by detection of the target by IHC or molecular assays), specimen requirements and how testing is performed, histologic aspects of response assessment, molecular monitoring of disease, and biologic and histopathologic aspects of secondary resistance, as relevant for each cancer setting. Topics, speakers and objectives for each talk are shown below.

AGENDA

Welcome & Introduction Marc Ladanyi, MD, Memorial Sloan-Kettering Cancer Center, New York, NY
Introduction & Overview of Targeted Therapies Charles Sawyers, MD, Memorial Sloan-Kettering Cancer Center, New York, NY
	To present an overview of the concept of targeted therapy, its historical milestones, the types of targeted therapy in current clinical use (drugs, antibodies), the types of pathways that are targeted, and current clinical indications and FDA-approved uses.
Leukemias James R. Downing MD, St. Jude Children's Research Hospital, Memphis, TN
	To discuss the experience with Gleevec in BCR-ABL-positive leukemias.
	To describe the rationale for targeting JAK2, NOTCH, and FLT3 in specific leukemias
	To review retinoic acid therapy for PML-RARA in APL.
Breast Carcinoma Allen Gown, MD, PhenoPath Laboratories, Seattle, WA
	To present an overview of the current status of ER/PR determination and hormonal therapy.
	To summarize HER2 biology and clinical correlations.
	To discuss the pros and cons and pitfalls of IHC and FISH in the determination of HER2 status, and to define accepted practice for HER2 status determination
Lung Carcinoma Marc Ladanyi, MD, Memorial Sloan-Kettering Cancer Center, New York, NY
	To provide an overview of EGFR biology and clinical correlations.
	To describe the pathologic correlates of EGFR mutations.
	To discuss the pros and cons and pitfalls of EGFR mutation detection vs EGFR FISH (or CISH) in the determination of EGFR status will be presented.
	To describe the criteria for selecting cases for EGFR testing and the pathologist's role in this process and the common methods for EGFR mutation analysis.
	To discuss primary and secondary resistance to EGFR inhibitors due to KRAS mutations and second EGFR mutations, respectively.
Colorectal Carcinoma Stanley R. Hamilton, MD, The University of Texas M.D. Anderson Cancer Center, Houston, TX
	To review the biological and clinical background on EGFR- and VEGFR-targeted drugs (cetuximab and bevacizumab).
	To discuss the role of EGFR IHC in therapy selection.
GIST and other sarcomas Cristina R. Antonescu, MD, Memorial Sloan-Kettering Cancer Center, New York, NY
	To review the experience with imatinib in GIST.
	To provide an overview of KIT and PDGFRA biology
	To present the clinical and pathologic correlates of different types of KIT mutations
	To discuss the role of KIT IHC vs mutation testing
	To present the pathologic features of imatinib treatment effect and imatinib resistance.
	To introduce another imatinib-responsive sarcoma (DFSP)
Thyroid Carcinoma Yuri Nikiforov, MD PhD, University of Pittsburgh, Pittsburgh, PA
	To describe the distinct oncogenic pathways to papillary thyroid carcinoma, including RET kinase activation by RET/PTC rearrangement, and activating point mutations in RAS or BRAF genes.
	To describe distinct subsets of follicular carcinomas characterized by the presence of a RAS mutation or of a PAX8-PPARgamma rearrangement.
	To explain the role of the pathologist in categorizing cases for targeted therapies by IHC (PPARgamma, RET) or mutation analysis (RAS, BRAF).
Prostate Carcinoma Mark Rubin, MD, Brigham and Women's Hospital/Harvard Medical School, Boston, MA
	To review androgen therapy, the histologic correlates of androgen ablation, and the features of androgen-independent prostate cancer.
	To discuss work on predictive markers for metastasis and androgen-independence.
	To discuss the emerging role of kinase inhibitors and other new targeted therapies under development.
Brain Tumors Paul Mischel, MD, David Geffen School of Medicine at UCLA, Los Angeles, CA
	To provide an overview of the major molecular alterations in gliomas (EGFR amplification, EGFRvIII mutant receptor, PTEN loss) and their roles as therapeutic targets.
	To discuss the role of EGFR IHC and FISH and other markers in the pathologic evaluation of gliomas.