乳腺癌靶向治疗.ppt

* basis of individualized therapy * * san antonio breast cancer symposium * * Targeted therapies for breast cancertowards individualized therapy * ppt课件 Focuses Current status and limitation Drug resistance and principles to conquer * ppt课件 Intrinsic subtypes of breast cancer 2011? St Gallen International Expert Consensus * ppt课件 HR-positive breast cancer (luminal A, B) Endocrine therapy One set of targeted therapies Neoadjuvant therapy, adjuvant therapy and metastatic disease Almost be weighted the same as chemotherapy * ppt课件 Limited by relapse of disease and development of resistance ＞50%?HR-positive?primary?breast?cancer?do?not?respond?to?first-line?endocrine?treatment?(primary?resistance) Many of the?sensitive?patients will?eventually?relapse?despite?an?initial?response?(acquired?resistance) * ppt课件 Mechanism 1 Cross-talk between ER and HER2 HER2?overexpression?confers?intrinsic?or?primary?resistance?to?endocrine?therapy * ppt课件 * ppt课件 Endocrine therapy + Herceptin (phase III TAnDEM study) Endocrine therapy + Lapatinib (anti-HER1/2 TKI) * ppt课件 Mechanism 2 Cross-talk between downstream of ER/HER2 PI3K/Akt/mTOR * ppt课件 * ppt课件 PI3K inhibitors Wortmannin, LY294002 activity of these PI3K inhibitors has been observed poor solubility, instability and high toxicity * ppt课件 Akt inhibitors Perifosine synthetic inhibitor which can prevent Akt recruitment to the membrane and block activation of downstream effectors good tolerance objective response rates are disappointing and insufficient * ppt课件 mTOR inhibitors Most highly investigated Rapamycin widely used as an immunosuppressant in organ transplants poor solubility and instability limited the application on breast cancer therapy * ppt课件 Temsirolimus (ToriselTM/CCI-779) approved by the FDA in 2007 for the intravenous treatment of metastatic renal cell carcinoma everolimus (CerticanTM/RAD001) Promising results reported in SABCS 2010 (Phase I study) * ppt课件 HER2 overexpression breast cancer Definitely Herceptin (t