PMID- 27737796
OWN - NLM
STAT- MEDLINE
DCOM- 20170329
LR  - 20211203
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 38
DP  - 2017 Feb
TI  - Strong synergism between small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 
      in human breast cancer cells.
PG  - 117-123
LID - S0887-2333(16)30209-0 [pii]
LID - 10.1016/j.tiv.2016.10.002 [doi]
AB  - Targeting pro-survival cell signaling components has been promising in cancer 
      therapy, but the benefit of targeting with single agents is limited. For 
      malignancies such as triple-negative breast cancer, there is a paucity of targets 
      that are amenable to existing interventions as they are devoid of the human 
      epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and 
      estrogen receptor (ER). Concurrent targeting of cell signaling entities other 
      than HER2, PR and ER with multiple agents may be more effective. Evaluating modes 
      of interaction between agents can inform efficient selection of agents when used 
      in cocktails. Using clonogenic cell survival, interaction between inhibitors of 
      HER2 (TAK-165), phosphoinositide 3-kinase (PI3K) and mammalian target of 
      rapamycin (mTOR) (NVP-BEZ235), and the pro-survival gene (Bcl-2) (ABT-263) in 
      three human breast cell lines (MDA-MB-231, MCF-7 and MCF-12A) ranged from strong 
      to very strong synergism. The strongest synergy was demonstrated in PR and ER 
      negative cells. Inhibition of PI3K, mTOR and Bcl-2 could potentially be effective 
      in the treatment of triple-negative cancers. The very strong synergy observed 
      even at lowest concentrations of inhibitors indicates that these cocktails might 
      be able to be used at a minimised risk of systemic toxicity. Concurrent use of 
      multiple inhibitors can potentiate conventional interventions like radiotherapy 
      and chemotherapy.
CI  - Copyright A(c) 2016 Elsevier B.V. All rights reserved.
FAU - Hamunyela, Roswita H
AU  - Hamunyela RH
AD  - Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, 
      Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 
      South Africa; Dr B May Cancer Care Centre, Ministry of Health and Social 
      Services, Windhoek, Namibia. Electronic address: hamunyela.rh@gmail.com.
FAU - Serafin, Antonio M
AU  - Serafin AM
AD  - Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, 
      Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 
      South Africa. Electronic address: ts@sun.ac.za.
FAU - Akudugu, John M
AU  - Akudugu JM
AD  - Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, 
      Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, 
      South Africa. Electronic address: jakudugu@sun.ac.za.
LA  - eng
PT  - Journal Article
DEP - 20161011
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Aniline Compounds)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Imidazoles)
RN  - 0 (Oxazoles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Quinolines)
RN  - 0 (Sulfonamides)
RN  - 0 (TAK-165)
RN  - 0 (Triazoles)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RUJ6Z9Y0DT (dactolisib)
RN  - XKJ5VVK2WD (navitoclax)
SB  - IM
MH  - Aniline Compounds/pharmacology
MH  - Antineoplastic Agents/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Breast Neoplasms
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Drug Synergism
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Oxazoles/pharmacology
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors
MH  - Quinolines/pharmacology
MH  - Receptor, ErbB-2/*antagonists & inhibitors
MH  - Sulfonamides/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Triazoles/pharmacology
OTO - NOTNLM
OT  - Small molecule inhibitor
OT  - Synergism
OT  - Triple-negative cancer
EDAT- 2016/10/21 06:00
MHDA- 2017/03/31 06:00
CRDT- 2016/10/15 06:00
PHST- 2016/03/30 00:00 [received]
PHST- 2016/08/15 00:00 [revised]
PHST- 2016/10/09 00:00 [accepted]
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2017/03/31 06:00 [medline]
PHST- 2016/10/15 06:00 [entrez]
AID - S0887-2333(16)30209-0 [pii]
AID - 10.1016/j.tiv.2016.10.002 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2017 Feb;38:117-123. doi: 10.1016/j.tiv.2016.10.002. Epub 2016 
      Oct 11.