肿瘤分子靶向治疗的思考.ppt

BATTLE PROGRAM Biomarker-based Approach of Targeted Therapy for Lung Cancer Elimination. Waun Ki Hong et al Biomarker Analysis in Core Biopsy ? Select Adequate Target Therapy 未来的方向 加强癌症基因分型及药物基因学研究，寻找各种靶向治疗药物的适用或预测指标。 Treating tumors according to their molecular defects and their upgraded or downgraded signal transduction pathways. Clinical Predictors of Gefitinib or Erlotinib Efficacy in NSCLC Never smoker Female gender Adenocarcinoma Bronchoalveolar adenocarcinoma Asian origin 肿瘤分子靶向治疗的思考 中山大学肿瘤防治所 管忠震 分子靶向治疗研究的兴起 上世纪70-80年代，癌症生物学研究迅速发展，从分子水平了解肿瘤发生、发展的机制。 Scientific research has increasingly identified key genetic events critical to specefic cancer development. Targeting Therapy A new generation of small molecules or MABs that rationaly designde to inhibit specific signal transduction or transcription pathways that are critical for cancer cell growth and survival. EGFR Blockade as Cancer therapy The EGFR autocrine pathways plays an important role in the development and progression of human epithelial cancer. EGFR activation triggers a cascade of signals leading to cell proliferation,production of antiogenic factors and promotion of invasion and metastasis. High expression of EGFR is common in a wide variety of human cancers and is generally associated with advanced disease and poor prognosis,and with resistance to hormone therapy,chemotherapy,or radiotherapy. EGFR Blockade as Cancer Therapy:J.mendelsohn’s Hypothesis (Early 1980s) The blockade of EGFR activation may inhibit cancr cell proliferation. Cancer cells may be selectively sensitive to EGFR inhibition as compared to normal cells. Selective anti-EGFR agents may be developed. 靶向治疗研究已获得明显成果 许多新的分子靶向药物仍在开发研究中 靶向治疗药物取得的成功 若干化疗无效（失败）的病例取得明显疗效 Iressa,Tarceva NSCLC Pt based chemo Failure Sorafenib,Sunibinib RCC,Refractory GIST Gleevec CML,GIST Herceptin Her2(+) Breast Ca Erbitux Chemo-re