Targeting Apoptotic Pathways in Acute Myeloid Leukaemia

被引：12

作者：

Sillar, Jonathan R. ^{[1
,2
,3
]}

Enjeti, Anoop K. ^{[2
,3
,4
]}

机构：

[1] Univ Newcastle, Sch Biomed Sci & Pharm, Callaghan, NSW 2308, Australia

[2] Calvary Mater Hosp Newcastle, Haematol Dept, Waratah, NSW 2298, Australia

[3] NSW Hlth Pathol North Hunter John Hunter Hosp, Newcastle, NSW 2305, Australia

[4] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia

来源：

CANCERS | 2019年 / 11卷 / 11期

关键词：

Acute Myeloid Leukaemia; programmed cell death; BCL-2; MCL-1; BH3; mimetic; apoptosis; BCL-2 ANTISENSE OLIGONUCLEOTIDE; PAN-BCL-2 FAMILY ANTAGONIST; BH3 MIMETIC ABT-737; CHRONIC LYMPHOCYTIC-LEUKEMIA; OBATOCLAX MESYLATE GX15-070; ACUTE MYELOGENOUS LEUKEMIA; PHASE-I; OLDER PATIENTS; AUTONOMOUS GROWTH; OPEN-LABEL;

D O I：

10.3390/cancers11111660

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute Myeloid Leukaemia is a devastating disease that continues to have a poor outcome for the majority of patients. In recent years, however, a number of drugs have received FDA approval, following on from successful clinical trial results. This parallels the characterization of the molecular landscape of Acute Myeloid Leukaemia (AML) over the last decade, which has led to the development of drugs targeting newly identified recurring mutations. In addition, basic biological research into the pathobiology of AML has identified aberrant programmed cell death pathways in AML. Following on from successful outcomes in lymphoid malignancies, drugs targeting the B Cell Lymphoma 2 (BCL-2) family of anti-apoptotic proteins have been explored in AML. In this review, we will outline the preclinical and clinical work to date supporting the role of drugs targeting BCL-2, with Venetoclax being the most advanced to date. We will also highlight rationale combinations using Venetoclax, ongoing clinical trials and biomarkers of response identified from the early phase clinical trials performed.

引用

页数：18

共 101 条

[21]

COTTER FE, 1994, ONCOGENE, V9, P3049

[22] Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma [J].

Davids, Matthew S. ;

Roberts, Andrew W. ;

Seymour, John F. ;

Pagel, John M. ;

Kahl, Brad S. ;

Wierda, William G. ;

Puvvada, Soham ;

Kipps, Thomas J. ;

Anderson, Mary Ann ;

Salem, Ahmed Hamed ;

Dunbar, Martin ;

Zhu, Ming ;

Peale, Franklin ;

Ross, Jeremy A. ;

Gressick, Lori ;

Desai, Monali ;

Kim, Su Young ;

Verdugo, Maria ;

Humerickhouse, Rod A. ;

Gordon, Gary B. ;

Gerecitano, John F. .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (08) :826-833

[23] BCL-2 PROTOONCOGENE EXPRESSION IN NORMAL AND NEOPLASTIC HUMAN MYELOID CELLS [J].

DELIA, D ;

AIELLO, A ;

SOLIGO, D ;

FONTANELLA, E ;

MELANI, C ;

PEZZELLA, F ;

PIEROTTI, MA ;

DELLAPORTA, G .

BLOOD, 1992, 79 (05) :1291-1298

[24]

Dennis M, 2017, BLOOD, V130

[25] Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML [J].

DiNardo, C. D. ;

Stein, E. M. ;

de Botton, S. ;

Roboz, G. J. ;

Altman, J. K. ;

Mims, A. S. ;

Swords, R. ;

Collins, R. H. ;

Mannis, G. N. ;

Pollyea, D. A. ;

Donnellan, W. ;

Fathi, A. T. ;

Pigneux, A. ;

Erba, H. P. ;

Prince, G. T. ;

Stein, A. S. ;

Uy, G. L. ;

Foran, J. M. ;

Traer, E. ;

Stuart, R. K. ;

Arellano, M. L. ;

Slack, J. L. ;

Sekeres, M. A. ;

Willekens, C. ;

Choe, S. ;

Wang, H. ;

Zhang, V. ;

Yen, K. E. ;

Kapsalis, S. M. ;

Yang, H. ;

Dai, D. ;

Fan, B. ;

Goldwasser, M. ;

Liu, H. ;

Agresta, S. ;

Wu, B. ;

Attar, E. C. ;

Tallman, M. S. ;

Stone, R. M. ;

Kantarjian, H. M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (25) :2386-2398

[26] Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies [J].

DiNardo, Courtney D. ;

Rausch, Caitlin R. ;

Benton, Christopher ;

Kadia, Tapan ;

Jain, Nitin ;

Pemmaraju, Naveen ;

Daver, Naval ;

Covert, Wendy ;

Marx, Kayleigh R. ;

Mace, Morgan ;

Jabbour, Elias ;

Cortes, Jorge ;

Garcia-Manero, Guillermo ;

Ravandi, Farhad ;

Bhalla, Kapil N. ;

Kantarjian, Hagop ;

Konopleva, Marina .

AMERICAN JOURNAL OF HEMATOLOGY, 2018, 93 (03) :401-407

[27] Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study [J].

DiNardo, Courtney L. ;

Pratz, Keith W. ;

Letai, Anthony ;

Jonas, Brian A. ;

Wei, Andrew H. ;

Thirman, Michael ;

Arellano, Martha ;

Frattini, Mark G. ;

Kantarjian, Hagop ;

Popovic, Relja ;

Chyla, Brenda ;

Xu, Tu ;

Dunbar, Martin ;

Agarwal, Suresh K. ;

Humerickhouse, Rod ;

Mabry, Mack ;

Potluri, Jalaja ;

Konopleva, Marina ;

Pollyea, Daniel A. .

LANCET ONCOLOGY, 2018, 19 (02) :216-228

[28] Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].

Doehner, Hartmut ;

Estey, Elihu ;

Grimwade, David ;

Amadori, Sergio ;

Appelbaum, Frederick R. ;

Buechner, Thomas ;

Dombret, Herve ;

Ebert, Benjamin L. ;

Fenaux, Pierre ;

Larson, Richard A. ;

Levine, Ross L. ;

Lo-Coco, Francesco ;

Naoe, Tomoki ;

Niederwieser, Dietger ;

Ossenkoppele, Gert J. ;

Sanz, Miguel ;

Sierra, Jorge ;

Tallman, Martin S. ;

Tien, Hwei-Fang ;

Wei, Andrew H. ;

Lowenberg, Bob ;

Bloomfield, Clara D. .

BLOOD, 2017, 129 (04) :424-447

[29] International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts [J].

Dombret, Herve ;

Seymour, John F. ;

Butrym, Aleksandra ;

Wierzbowska, Agnieszka ;

Selleslag, Dominik ;

Jang, Jun Ho ;

Kumar, Rajat ;

Cavenagh, James ;

Schuh, Andre C. ;

Candoni, Anna ;

Recher, Christian ;

Sandhu, Irwindeep ;

Bernal del Castillo, Teresa ;

Al-Ali, Haifa Kathrin ;

Martinelli, Giovanni ;

Falantes, Jose ;

Noppeney, Richard ;

Stone, Richard M. ;

Minden, Mark D. ;

McIntyre, Heidi ;

Songer, Steve ;

Lucy, Lela M. ;

Beach, C. L. ;

Doehner, Hartmut .

BLOOD, 2015, 126 (03) :291-299

[30] Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions [J].

Fischer, K. ;

Al-Sawaf, O. ;

Bahlo, J. ;

Fink, A. -M. ;

Tandon, M. ;

Dixon, M. ;

Robrecht, S. ;

Warburton, S. ;

Humphrey, K. ;

Samoylova, O. ;

Liberati, A. M. ;

Pinilla-Ibarz, J. ;

Opat, S. ;

Sivcheva, L. ;

Du, K. Le ;

Fogliatto, L. M. ;

Niemann, C. U. ;

Weinkove, R. ;

Robinson, S. ;

Kipps, T. J. ;

Boettcher, S. ;

Tausch, E. ;

Humerickhouse, R. ;

Eichhorst, B. ;

Wendtner, C. -M. ;

Langerak, A. W. ;

Kreuzer, K. -A. ;

Ritgen, M. ;

Goede, V. ;

Stilgenbauer, S. ;

Mobasher, M. ;

Hallek, M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2019, 380 (23) :2225-2236

← 1 2 3 4 5 6 7 8 9 10 →