9 Tumor+Chemotherapy English +Version Imp
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9 Tumor+Chemotherapy English +Version Imp
- 1. Tumor Chemotherapy Sun Yet-san University Cancer Center Rui-Hua Xu, Zhi-Ming Li E-mail: xurh@mail.sysu.edu.cn [email_address] Tel: 8734 3356
- 5. Development of Chemo-drugs Nitrogen Mustard for lymphoma 40s 50s MTX for hematological malignancies & children’s ALL 70s DDP 、 ADM—palliative chemotherapy transition to curative chemotherapy, medical oncology established 80s Adjuvant/Neo-adjuvant chemotherapy 90s 21 st Biological Response Modifier ， supportive care ， High dose chemotherapy ＋ HSCT Molecular target drug
- 15. 时间 指数生长 癌瘤 正常 细胞产生 = 细胞丢失 稳定态 Gompertzian 生长 对数细胞数 时间 指数生长 癌瘤 正常 细胞产生 = 细胞丢失 稳定态 Gompertzian 生长 对数细胞数 时间 指数生长 癌瘤 正常 细胞产生 = 细胞丢失 稳定态 Gompertzian 生长 对数细胞数 Time Exponential Growth tumor normal cell produce=cell loss Stable state Gompertzian growth cell produce > cell loss l Log of Cells
- 22. NEJM 2003 348:538-549 Target enzyme and efficacy of anticancer drug
- 23. Clin Cancer Res 4139 2006;12(14) July 15, 2006
- 27. Cell cycle non-specific agents 100 S 细 胞 存 活 R 率 % 剂量 S: Slow growth (normal cell) R: Rapid growth (tumor cell)
- 28. Cell cycle specific agents 100 S 细 胞 存 活 R 率 % 剂量 S: Slow growth (normal cell) R: Rapid growth (tumor cell)
- 34. Platinum drugs Pt(II) NH 3 NH 3 Pt(II) NH 3 NH 3 + 2H 2 O Cisplatin Reactive complex + 2Cl - Pt G G Cl Cl H 2 O + H 2 O + DNA Strand
- 38. Anti-metabolite anticancer drugs Dihydrofolate Reductase METHOTREXATE (MTX) FH 2 FH 4 Uracil + N 5-10 methylene FH 4 deoxynucleotide （ dUMP ） 5- fluorouracil (5-FU) Purine Nucleotide thymidine deoxynucleotide (dTMP) Thymidylate Synthase (TS) fluorouracil deoxynucleotide （ F dUMP ） DNA DNApolymerase Cytarabine (Arac) Gemcitabine 6MP 、 6TG
- 39. Antibiotic anticancer drugs Double strand dissociation Interfere DNA transcription and mRNA synthesis Anthracycline antibotics insert to the base pair near the DNA double strand
- 43. Tubulin inhibitor Interfere tubulin polymerization : colchicine Vinblastine block tubulin depolymerization : Taxoids tubulin tubule 20nm
- 48. Topoisomerase Attached double-stranded DNA ， cut through the DNA strand transiently ， the torsion disappeared ， then catch the rotated DNA again ， re-adhesion the DNA strand
- 49. Topoisomerase I inhibitors Topoisomerase I inhibitors combined with TOPO I-DNA complex
- 50. Topoisomerase I inhibitors combination of replication fork & Breaking of DNA single strand Interruption of the cell cycle Cell death
- 51. Mechanism of anticancer drugs
- 53. Common target drugs Name Trade name Main targets Structure Indication Imatinib Gleeve Bcr/Abl, c-kit, PDEFR Small Molecule Compounds CML GIST Retuximab MabThera CD-20( B limphocyte) Chimeric Antibody NHL Transtuzumab Herceptin HER2/neu Human antibody Breast cancer Gefitinib Iressa EGFR-TK Small Molecule Compounds NSCLC Cetuximab Erbitux EGFR Chimeric Antibody Colorectal, head & neck Erlotinib Tarceva EGFR-TK Small Molecule Compounds 非小细胞肺癌 NSCLC Bevacizumab Avastin VEGF Human antibody Colorectal Ca
- 54. Gefitinib erlotinib Anti-EGFR 2: Herceptin Anti-EGFR 1: Cetuximub
- 66. Balance of c hemotherapy efficacy and toxicity Efficacy Safety Strategy for the reasonable application of chemotherapy
- 67. Patient’s survival time and quality of life after treatment
- 71. PROGRESS IN MEDICAL ONCOLOGY 1975 -> 2000 -> 2025 MOLECULAR MEDICINE EVIDENCE-BASED MEDICINE SMALL, PILOT TRIALS P R O G R E S S 1975 1980 2000
- 73. Thank you!
Notas del editor
- electrophiles
- 2 2 Simplified diagram of the EGFR pathway consisting of the EGFR signal transduction cascade, and cellular effects of stimulation through the EGFR. 5 The ligand binding site serves as the receptor for ligands such as EGF and TGF- Upon ligand binding, subsequent receptor signaling, including autophosphorylation of the receptor and phosphorylation of target proteins, occurs downstream in the signal transduction cascade. 2 • EGFR is expressed in a significant percentage of human tumors. Expression has been correlated with poor prognosis, decreased survival, and/or increased metastases. 2 • EGFR plays a critical role in cellular growth, repair, and survival and has been demonstrated to function as a key pathway for the regulation of growth in many tumor types. 2 • Current therapies have significant therapeutic and safety limitations in the management of solid tumors. The use of EGFR targeted therapy is a potentially important addition to standard anticancer therapy. 2 • It has been postulated that EGFR inhibitors may synergize with radiation and certain chemotherapeutic agents, possibly through apoptotic, antiangiogenic, and/or cell cycle effects. 2