AIMS: To outline the progress being made in the understanding of acquired resistance to long term therapy with the selective oestrogen receptor modulators (SERMs, tamoxifen and raloxifene) and aromatase inhibitors. The question to be addressed is how we can amplify the new biology of oestrogen-induced apoptosis to create more complete responses in exhaustively antihormone treated metastatic breast cancer. METHODS AND RESULTS: Three questions are posed and addressed. (1) Do we know how oestrogen works? (2) Can we improve adjuvant antihormonal therapy? (3) Can we enhance oestrogen-induced apoptosis? The new player in oestrogen action is GPR30 and there are new drugs specific for this target to trigger apoptosis. Similarly, anti-angiogenic drugs can be integrated into adjuvant antihormone therapy or to enhance oestrogen-induced apoptosis in Phase II antihormone resistant breast cancer. The goal is to reduce the development of acquired antihormone resistance or undermine the resistance of breast cancer cells to undergo apoptosis with oestrogen respectively. Finally, drugs to reduce the synthesis of glutathione, a subcellular molecule compound associated with drug resistance, can enhance oestradiol-induced apoptosis. CONCLUSIONS: We propose an integrated approach for the rapid testing of agents to blunt survival pathways and amplify oestrogen-induced apoptosis and tumour regression in Phase II resistant metastatic breast cancer. This Pharma platform will provide rapid clinical results to predict efficacy in large scale clinical trials.
AIMS: To outline the progress being made in the understanding of acquired resistance to long term therapy with the selective oestrogen receptor modulators (SERMs, tamoxifen and raloxifene) and aromatase inhibitors. The question to be addressed is how we can amplify the new biology of oestrogen-induced apoptosis to create more complete responses in exhaustively antihormone treated metastatic breast cancer. METHODS AND RESULTS: Three questions are posed and addressed. (1) Do we know how oestrogen works? (2) Can we improve adjuvant antihormonal therapy? (3) Can we enhance oestrogen-induced apoptosis? The new player in oestrogen action is GPR30 and there are new drugs specific for this target to trigger apoptosis. Similarly, anti-angiogenic drugs can be integrated into adjuvant antihormone therapy or to enhance oestrogen-induced apoptosis in Phase II antihormone resistant breast cancer. The goal is to reduce the development of acquired antihormone resistance or undermine the resistance of breast cancer cells to undergo apoptosis with oestrogen respectively. Finally, drugs to reduce the synthesis of glutathione, a subcellular molecule compound associated with drug resistance, can enhance oestradiol-induced apoptosis. CONCLUSIONS: We propose an integrated approach for the rapid testing of agents to blunt survival pathways and amplify oestrogen-induced apoptosis and tumour regression in Phase II resistant metastatic breast cancer. This Pharma platform will provide rapid clinical results to predict efficacy in large scale clinical trials.
Authors: Victor G Vogel; Joseph P Costantino; D Lawrence Wickerham; Walter M Cronin; Reena S Cecchini; James N Atkins; Therese B Bevers; Louis Fehrenbacher; Eduardo R Pajon; James L Wade; André Robidoux; Richard G Margolese; Joan James; Scott M Lippman; Carolyn D Runowicz; Patricia A Ganz; Steven E Reis; Worta McCaskill-Stevens; Leslie G Ford; V Craig Jordan; Norman Wolmark Journal: JAMA Date: 2006-06-05 Impact factor: 56.272
Authors: Bernard Fisher; Joseph P Costantino; D Lawrence Wickerham; Reena S Cecchini; Walter M Cronin; Andre Robidoux; Therese B Bevers; Maureen T Kavanah; James N Atkins; Richard G Margolese; Carolyn D Runowicz; Joan M James; Leslie G Ford; Norman Wolmark Journal: J Natl Cancer Inst Date: 2005-11-16 Impact factor: 13.506
Authors: P E Lønning; P D Taylor; G Anker; J Iddon; L Wie; L M Jørgensen; O Mella; A Howell Journal: Breast Cancer Res Treat Date: 2001-05 Impact factor: 4.872
Authors: Silvana Martino; Jane A Cauley; Elizabeth Barrett-Connor; Trevor J Powles; John Mershon; Damon Disch; Roberta J Secrest; Steven R Cummings Journal: J Natl Cancer Inst Date: 2004-12-01 Impact factor: 13.506
Authors: Angelo Di Leo; Henry L Gomez; Zeba Aziz; Zanete Zvirbule; Jose Bines; Michael C Arbushites; Stephanie F Guerrera; Maria Koehler; Cristina Oliva; Steven H Stein; Lisa S Williams; Judy Dering; Richard S Finn; Michael F Press Journal: J Clin Oncol Date: 2008-10-27 Impact factor: 44.544
Authors: Rui Xiong; Hitisha K Patel; Lauren M Gutgesell; Jiong Zhao; Loruhama Delgado-Rivera; Thao N D Pham; Huiping Zhao; Kathryn Carlson; Teresa Martin; John A Katzenellenbogen; Terry W Moore; Debra A Tonetti; Gregory R J Thatcher Journal: J Med Chem Date: 2015-12-30 Impact factor: 7.446
Authors: Roshani R Patel; Surojeet Sengupta; Helen R Kim; Andres J Klein-Szanto; Jennifer R Pyle; Fang Zhu; Tianyu Li; Eric A Ross; Salewa Oseni; Joseph Fargnoli; V Craig Jordan Journal: Eur J Cancer Date: 2010-03-18 Impact factor: 9.162
Authors: Melyssa R Bratton; Elizabeth C Martin; Steven Elliott; Lyndsay V Rhodes; Bridgette M Collins-Burow; John A McLachlan; Thomas E Wiese; Stephen M Boue; Matthew E Burow Journal: J Steroid Biochem Mol Biol Date: 2015-03-12 Impact factor: 4.292
Authors: H Iwase; Y Yamamoto; M Yamamoto-Ibusuki; K-I Murakami; Y Okumura; S Tomita; T Inao; Y Honda; Y Omoto; K-I Iyama Journal: Br J Cancer Date: 2013-09-03 Impact factor: 7.640