Synergistic induction of cell death in haematological malignancies by combined phosphoinositide-3-kinase and BET bromodomain inhibition

British Journal of Haematology

Volumn 170, Issue 2, 2015, Pages 275-278

  Tinsley, Steven ^a   Meja, Koremu ^a   Shepherd, Clare ^a   Khwaja, Asim ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Apoptosis; Bromodomain containing 4; JQ1; MYC; PI3K

Indexed keywords

ANTINEOPLASTIC AGENT; BRD4 PROTEIN, HUMAN; NUCLEAR PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE INHIBITOR; TRANSCRIPTION FACTOR;

ANTAGONISTS AND INHIBITORS; CELL DEATH; DRUG EFFECTS; DRUG POTENTIATION; HEMATOLOGIC NEOPLASMS; HUMAN; METABOLISM;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL DEATH; DRUG SYNERGISM; HEMATOLOGIC NEOPLASMS; HUMANS; NUCLEAR PROTEINS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; TRANSCRIPTION FACTORS;

EID: 84934437192     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.13283     Document Type: Letter

References (10)

1. Dang, C.V. (2012) MYC on the path to cancer. Cell, 149, 22-35.
2. Dawson, M.A., Kouzarides, T. & Huntly, B.J. (2012) Targeting epigenetic readers in cancer. New England Journal of Medicine, 367, 647-657.
3. Delmore, J.E., Issa, G.C., Lemieux, M.E., Rahl, P.B., Shi, J., Jacobs, H.M., Kastritis, E., Gilpatrick, T., Paranal, R.M., Qi, J., Chesi, M., Schinzel, A.C., McKeown, M.R., Heffernan, T.P., Vakoc, C.R., Bergsagel, P.L., Ghobrial, I.M., Richardson, P.G., Young, R.A., Hahn, W.C., Anderson, K.C., Kung, A.L., Bradner, J.E. & Mitsiades, C.S. (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell, 146, 904-917.
4. Faber, A.C., Ebi, H., Costa, C. & Engelman, J.A. (2012) Apoptosis in targeted therapy responses: the role of BIM. Advances in Pharmacology, 65, 519-542.
5. Fruman, D.A. & Rommel, C. (2014) PI3K and cancer: lessons, challenges and opportunities. Nature Reviews Drug Discovery, 13, 140-156.
6. Klempner, S.J., Myers, A.P. & Cantley, L.C. (2013) What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway. Cancer Discovery, 3, 1345-1354.
7. Loven, J., Hoke, H.A., Lin, C.Y., Lau, A., Orlando, D.A., Vakoc, C.R., Bradner, J.E., Lee, T.I. & Young, R.A. (2013) Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell, 153, 320-334.
8. Meja, K., Stengel, C., Sellar, R., Huszar, D., Davies, B.R., Gale, R.E., Linch, D.C. & Khwaja, A. (2014) PIM and AKT kinase inhibitors show synergistic cytotoxicity in acute myeloid leukaemia that is associated with convergence on mTOR and MCL1 pathways. British Journal of Haematology, 167, 69-79.
9. Shepherd, C., Banerjee, L., Cheung, C.W., Mansour, M.R., Jenkinson, S., Gale, R.E. & Khwaja, A. (2013) PI3K/mTOR inhibition upregulates NOTCH-MYC signalling leading to an impaired cytotoxic response. Leukemia, 27, 650-660.
10. Zuber, J., Shi, J., Wang, E., Rappaport, A.R., Herrmann, H., Sison, E.A., Magoon, D., Qi, J., Blatt, K., Wunderlich, M., Taylor, M.J., Johns, C., Chicas, A., Mulloy, J.C., Kogan, S.C., Brown, P., Valent, P., Bradner, J.E., Lowe, S.W. & Vakoc, C.R. (2011) RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature, 478, 524-528.