文档介绍：第2届广州国际肺癌论坛
2011年8月20日, 广州
蒋国梁
复旦大学附属肿瘤医院
非小细胞肺癌的放射和吉非替尼综合治疗
e of non-small cell carcinoma
Stage and tmt 5-yr survival
I-II surgery 48-70%
I-II inoperable, SBRT ~40%
IIIa (surgery ±other Tmt) 15-27%
IIIa (RT+Chemo) 14-20%
IIIb (RT+Chemo) 5-7%
进一步提高非小细胞肺癌的疗效:放疗+靶向药物治疗
Gefitinib enhanced radiosensitivity of tumor cells Survival curve of Oral SCC (in vitro)
Shintani S. Int J Cancer 2003; 107:1030–37
Shoulder of survival curve disappear (inhibition for SLD repair)
Slop of survival curve reduced (intrinsic radiosensitivity increased)
Gefitinib enhanced radiosensitivity of tumor cells
GEO (rectal carcinoma) in vivo (tumor re-growth delay)
10Gy/fx×4fx + Iressa ip d1-5×4 wks
Bianco et al. Clin Cancer Res 2002;8:3250-3258
Iressa + RT
Control
RT
Iressa
The percentage of S phase decreased after Iressa Iressa+RT (GEO in vivo)
Bianco C. Clin Cancer Res 2002;8:3250-3258
Mechanism of Gefitinib radiosensitization
Gefitinib speeds up apoptosis of tumor cells after RT GEO in vivo
Bianco C. Clin Cancer Res 2002;8:3250-3258
RT+Iressa
RT
Iressa
Gefitinib inhibits RT induced damage repair Oral SCC (Western blot)
Shintani S. et al. Int J Cancer 2003; 107:1030–1037
RT damage DNA
Need DNA repair enzyme
RT enzyme DNA repair
Gefitinib enzyme DNA repair
Iressa+RT in Oral SCC (Western blot)
RT could activate EGFR-TK signaling pathway (Ras-Raf-MAPK). And initiates a multistep phosphorylation cascade that leads to activation the pathway, and stimulates cell-cycle progression
Shintani S. Int J Cancer 2003; 107:1030–1037
Gefitinib could inhibit multistep phosphorylation of EGFR signaling pathway, so slow down the tumor cell proliferation and enhance the radiation sterilization.
Possible mechanisms for radiosensitization of Gefitinib
Decrease percentage of S phase and increase G2/M phases of tumor cells
Enhance tumor cell apoptosis after RT
Inhibit radiation induced DNA repair
Inhibit multistep phosphorylation of EGFR signaling pathway, so redu