nach oben

Breast Cancer Research

Erschienen in:

01.10.2013 | Viewpoint

Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER⁺ breast cancer

verfasst von: Jing Deng, Anthony Letai

Erschienen in: Breast Cancer Research | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

The B-cell lymphoma/leukemia 2 protein (BCL-2) may help many types of cancers to evade cell death. However, identifying exactly where this is the case is a challenge. ABT-199 is a small molecule that selectively inhibits BCL-2, which is currently in clinical trials in lymphoid malignancies. While inhibiting BCL-2 by itself can cause cell death in hematopoietic tumors, single-agent activity is harder to observe in solid tumors. Combining ABT-199 with tamoxifen, the standard endocrine therapy for estrogen receptor-positive breast cancers, 85% of which have BCL-2 expression, represents a new strategy to prime cancer cells for apoptosis and elicit better cancer cell death responses.

Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral

Ring A, Dowsett M: Mechanisms of tamoxifen resistance. Endocr Relat Cancer. 2004, 11: 643-658. 10.1677/erc.1.00776.CrossRefPubMed

Musgrove EA, Sutherland RL: Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009, 9: 631-643. 10.1038/nrc2713.CrossRefPubMed

Vaillant F, Merino D, Lee L, Breslin K, Pal B, Ritchie ME, Smyth GK, Christie M, Phillipson LJ, Burns CJ, Mann GB, Visvader JE, Lindeman GJ: Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell. 2013, 24: 120-129. 10.1016/j.ccr.2013.06.002.CrossRefPubMed

Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O’Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH: An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005, 435: 677-681. 10.1038/nature03579.CrossRefPubMed

Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson EF, Marsh KC, Mitten MJ, Nimmer P, Roberts L, Tahir SK, Xiao Y, Yang X, Zhang H, Fesik S, Rosenberg SH, Elmore SW: ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008, 68: 3421-3428. 10.1158/0008-5472.CAN-07-5836.CrossRefPubMed

Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, Carney DA, He SZ, Huang DC, Xiong H, Cui Y, Busman TA, McKeegan EM, Krivoshik AP, Enschede SH, Humerickhouse R: Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012, 30: 488-496. 10.1200/JCO.2011.34.7898.CrossRefPubMed

Wilson WH, O’Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, Tulpule A, Dunleavy K, Xiong H, Chiu YL, Cui Y, Busman T, Elmore SW, Rosenberg SH, Krivoshik AP, Enschede SH, Humerickhouse RA: Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010, 11: 1149-1159. 10.1016/S1470-2045(10)70261-8.CrossRefPubMedPubMedCentral

Davids MS, Letai A: ABT-199: taking dead aim at BCL-2. Cancer Cell. 2013, 23: 139-141. 10.1016/j.ccr.2013.01.018.CrossRefPubMedPubMedCentral

10.

Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, Khaw SL, Kovar PJ, Lam LT, Lee J, Maecker HL, Marsh KC, Mason KD, Mitten MJ, Nimmer PM, Oleksijew A, Park CH, Park CM, Phillips DC, Roberts AW, Sampath D, Seymour JF, Smith ML, et al: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013, 19: 202-208. 10.1038/nm.3048.CrossRefPubMed

11.

Vogler M, Dinsdale D, Dyer MJ, Cohen GM: ABT-199 selectively inhibits BCL2 but not BCL2L1 and efficiently induces apoptosis of chronic lymphocytic leukaemic cells but not platelets. Br J Haematol. 2013, 163: 139-142. 10.1111/bjh.12457.CrossRefPubMed

12.

Dawson SJ, Makretsov N, Blows FM, Driver KE, Provenzano E, Le Quesne J, Baglietto L, Severi G, Giles GG, McLean CA, Callagy G, Green AR, Ellis I, Gelmon K, Turashvili G, Leung S, Aparicio S, Huntsman D, Caldas C, Pharoah P: BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer. 2010, 103: 668-675. 10.1038/sj.bjc.6605736.CrossRefPubMedPubMedCentral

13.

Oakes SR, Vaillant F, Lim E, Lee L, Breslin K, Feleppa F, Deb S, Ritchie ME, Takano E, Ward T, Fox SB, Generali D, Smyth GK, Strasser A, Huang DC, Visvader JE, Lindeman GJ: Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737. Proc Natl Acad Sci U S A. 2012, 109: 2766-2771. 10.1073/pnas.1104778108.CrossRefPubMed

14.

Del Gaizo MV, Brown JR, Certo M, Love TM, Novina CD, Letai A: Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007, 117: 112-121. 10.1172/JCI28281.CrossRef

15.

Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A: BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 2007, 12: 171-185. 10.1016/j.ccr.2007.07.001.CrossRefPubMed

Titel: Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer
verfasst von: Jing Deng
Anthony Letai
Publikationsdatum: 01.10.2013
Verlag: BioMed Central
Erschienen in: Breast Cancer Research / Ausgabe 5/2013
Elektronische ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr3568

Springer Medizin

Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER⁺ breast cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2013

Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women

Therapeutic targeting of erbB3 with MM-121/SAR256212 enhances antitumor activity of paclitaxel against erbB2-overexpressing breast cancer

Help us find the cures

A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model

Decision aids for breast cancer chemoprevention

Pre-diagnosis oophorectomy, estrogen therapy and mortality in a cohort of women diagnosed with breast cancer

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie