Title: PATH 6266: NEOPLASIA
1PATH 6266 NEOPLASIA
- Neoplasia
- The new and abnormal development of cells that
may be benign or malignant - Malignant Tumors
- Carcinoma
- Breast Cancer, colon cancer, prostate cancer
- Sarcoma
- Liposarcoma
- Osteosarcoma
- Chondrosarcoma
- Leimyosarcoma, rhabdomyosarcoma
- Lymphoma
- Diffuse large B cell lymphoma (T cell, B-Cell)
- Hodgkin lymphoma
- Leukemia
- Acute lymphoblastic leukemia
- CML t(9 22) (BCR-ABL)
- AML-M3 t(15 17) (PML/RARa)
- Multiple myeloma
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31Molecular Classification of Breast Cancer
RT-PCR using cDNA array of more than 500 genes
32Luminal HER-2 Basal-Like
Expression Patterns High expression of hormone receptors and associated genes (Lum A gt Lum B) High expression of HER2 and other genes in amplicon Low expression of ER and associated genes High expression of basal epithelial genes, basal CKs Low expression of ER and associated genes Low expression of HER2
Clinical Features 70 of breast cancers ER/PR positive Lum B tend to be higher grade than Lum A Some overexpress HER2 (Lum B) 15 of breast cancers ER/PR negative More likely high grade and node 15 of breast cancers ER/PR/HER2 negative BRCA1-associated cancers Metastasize hematogenously, brain and lung, less likely to axillary lymph node
Treatment Response Outcome Respond to endocrine therapy (may differ for Lum A and Lum B) Response to chemo variable (? Lum B gt Lum A) Good prognosis Respond to Herceptin Respond to anthracycline-based chemo Poor prognosis No response to endocrine therapy or Herceptin ? Response to platinum Poor prognosis
33Targeted Molecular Therapy
- Gleevec STI 571 (Imatinib mesylate)
- Chronic myeloid leulemia (CML)
- BCR-ABL
- Gastrointestinal stromal tumor (GIST)
- C-KIT mutation (80-90 of GIST)
- Exon 11 67-83 response rate
- Exon 9 40 response rate
- Platelet-derived growth factor-a receptor (2 of
the GIST) - No known tyrasine kinase mutation 11
- 32 response rate to imatinib
A Kit exon 11 mutation was the single best
predictor of an objective response to Imatinib.
34Molecular Therapy
- Colon Cancer
- KRAS 30
- BRAF 10
- MSI
35Molecular Therapy
- Breast Cancer
- 20 Her2/neu
- Worse prognosis
- Improved survival
36EMT
- Epithelial Mesenchymal Transition
- Inflammatory cytokines
- E-Cadherin
- Reverse of EMT
- COX-2 inhibitor
37Cancer Ste Cells
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