Fudan University Shanghai cancer Center 《 Basic clinical oncology》 Principles of Molecularly Targeted Therapy: Present and Future Fudan University Cancer center Guo Ye. MD Arrrr 复旦大学上海医学院肿瘤学糸
1 复旦大学上海医学院肿瘤学系 Fudan University Shanghai Cancer Center 《Basic Clinical Oncology》 Principles of Molecularly Targeted Therapy: Present and Future Fudan University Cancer Center Guo Ye, MD
Fudan University shanghai cancer center Self-introduction Name: Guo Ye, MD(Patrick Guo Institute: Fudan University Shanghai Cancer Center Major: Medical Oncologist Specialty: lymphoma, Head neck cancer Overseas training: Department of Hematology-Oncology, National University Hospital, Singapore( Clinical Fellowship) E-mailaddresspattrickguo@gmail.com 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 2 Self-introduction ▪ Name: Guo Ye, MD (Patrick Guo) ▪ Institute: Fudan University Shanghai Cancer Center ▪ Major: Medical Oncologist ▪ Specialty: lymphoma, Head & neck cancer ▪ Overseas training: Department of Hematology-Oncology, National University Hospital, Singapore (Clinical Fellowship) ▪ E-mail address: pattrickguo@gmail.com Fudan University Shanghai Cancer Center
Fudan University Shanghai cancer Center Mainstay Treatment Strategies Surgery Radiotherapy Chemotherapy Targeted therapy -- personalized therapy 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 3 Mainstay Treatment Strategies ▪ Surgery ▪ Radiotherapy ▪ Chemotherapy ▪ Targeted therapy --- personalized therapy
Fudan University Shanghai cancer Center Disadvantages of Cytotoxic Chemotherapy Non-selective Substantial and cumulative side effects Immunosuppressive Maintenance usually Impossible ■| convenient Mostly intravenous Frequent hospital visits 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 4 Disadvantages of Cytotoxic Chemotherapy ▪ Non-selective ▪ Substantial and cumulative side effects ▪ Immunosuppressive ▪ Maintenance usually impossible ▪ Inconvenient ﹣Mostly intravenous ﹣Frequent hospital visits
Fudan University Shanghai cancer Center Hallmarks of cancer Sustaining proliferative signaling Resisting Evading growth cell death suppressors Inducing Activating invasion oogenesiS and metastasis Enabling replicative mmortality 复旦大学上海医学院肿瘤学糸 Hanahan D, et al. Cell. 2000: 100: 57
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 5 Hallmarks of Cancer Hanahan D, et al. Cell. 2000;100:57
Fudan University Shanghai cancer Center Therapeutic Targets of Cancer EGFR Cyclin-dependent inhibitors kinase inhibitors Sustaining Aerobic glycolysis proliferative Immune activating inhibitors suppressors anti-CTLA4 mAb Deregulating Avoiding cellular mmune energetic Proapoptotic Resisting ase BH3 mimetics =← Inhibitors nstability promoting inflammation PARP Activating Selective anti- inhibitors inflammatory drugs Inhibitors of Inhibitors of VEGF signaling HGF/C-Met 复旦大学上海医学院肿瘤学糸 Hanahan. et al. Cell 2011: 144: 646
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 6 Therapeutic Targets of Cancer Hanahan D, et al. Cell. 2011;144:646
Fudan University Shanghai cancer Center Proved and Actively Tested Targets Ligand-targeted apeutic Therapy Antibodies ± Toxins Metalloproteinase Inhibitors Growth Antigens Factor Receptors Immunotherapy Tyrosine Kinase Inhibitors(Glivec, Gefitinib Cancer Intracellular Cell Signaling Molecules Apoptosis Agonists m-RNA Antisense Angiogenesis Inhibitors (Angiostatin, Endostatin& Avastin) 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 7 Proved and Actively Tested Targets
Fudan University Shanghai cancer Center Molecular Targets BCR-ABL chronic myeloid leukemia(CML) EGFR(Epidermal Growth Factor Receptor) non-small-cell lung cancer(NSCLC), colorectal cancer, head neck cancer ■HER2 breast cancer, gastric cancer VEGF (vascular endothelial growth factor) non-small-cell lung cancer(NSCLC), colorectal cancer, renal cell cancer(RCC) - CD20 B-cell lymphoma 8 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 8 Molecular Targets ▪ BCR-ABL ﹣ chronic myeloid leukemia (CML) ▪ EGFR (Epidermal Growth Factor Receptor) ﹣ non-small-cell lung cancer (NSCLC), colorectal cancer, head & neck cancer ▪ HER2 ﹣ breast cancer, gastric cancer ▪ VEGF (vascular endothelial growth factor) ﹣ non-small-cell lung cancer (NSCLC), colorectal cancer, renal cell cancer (RCC) ▪ CD20 ﹣ B-cell lymphoma
Fudan University Shanghai cancer Center Types of Targeted Agents Tyrosine kinase receptor inhibitors gefitinib, erlotinib, sunitinib, sorafenib Angiogenesis inhibitors sunitinib. sorafenib, bevacizumab Proteasome inhibitors Immunotherapy(monoclonal antibodies) cetuximab, trastuzumab, rituximab 9 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 9 Types of Targeted Agents ▪ Tyrosine kinase receptor inhibitors ﹣gefitinib, erlotinib, sunitinib, sorafenib ▪ Angiogenesis inhibitors ﹣sunitinib, sorafenib, bevacizumab ▪ Proteasome inhibitors ▪ Immunotherapy (monoclonal antibodies) ﹣cetuximab, trastuzumab, rituximab
Fudan University shanghai cancer Center Molecular Target: BCR-ABL 10 复旦大学上海医学院肿瘤学糸
Fudan University Shanghai Cancer Center 复旦大学上海医学院肿瘤学系 10 Molecular Target: BCR-ABL