PMID- 22923165
OWN - NLM
STAT- MEDLINE
DCOM- 20130307
LR  - 20211203
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 7
IP  - 3
DP  - 2012 Sep
TI  - Resistance to targeted therapies in pancreatic neuroendocrine tumors (PNETs): 
      molecular basis, preclinical data, and counteracting strategies.
PG  - 173-81
LID - 10.1007/s11523-012-0229-6 [doi]
AB  - Management of advanced pancreatic neuroendocrine tumors (PNETs) is challenging. 
      Chemotherapy has remained for decades the only validated therapeutic option, with 
      debated efficacy. Recently, data from two large placebo-controlled phase III 
      trials have demonstrated that targeted therapies directed against receptor of 
      vascular endothelial growth factor (sunitinib) and mammalian target of rapamycin 
      (mTOR) (everolimus) produced clinically significant improvement in patients with 
      advanced PNETs, resulting in a doubling of progression free survival and leading 
      to their FDA approval. However, as more patients have been treated following the 
      approval of those drugs, reports of early progression, and tumor regrowth 
      following initial responses strongly suggested that primary and acquired 
      resistances may limit the efficacy of targeted therapies in PNETs. In this 
      review, we aim to summarize the current knowledge about primary and acquired 
      resistance to targeted therapies, i.e., antiangiogenic agents and mTOR 
      inhibitors, using data available from preclinical and clinical studies in various 
      malignancies. Herein, we also describe how these general mechanisms of resistance 
      may emerge in PNETs in patients treated with sunitinib and everolimus. Overcoming 
      such resistances is likely to be the next challenge for clinicians in advanced 
      PNETs management, warranting seeking for new anticancer strategies.
FAU - Tijeras-Raballand, Annemilai
AU  - Tijeras-Raballand A
AD  - Pre Clinical Department, AAREC Filia Research, Boulogne-Billancourt, France. 
      araballand@aarec-filia-research.com
FAU - Neuzillet, Cindy
AU  - Neuzillet C
FAU - Couvelard, Anne
AU  - Couvelard A
FAU - Serova, Maria
AU  - Serova M
FAU - de Gramont, Armand
AU  - de Gramont A
FAU - Hammel, Pascal
AU  - Hammel P
FAU - Raymond, Eric
AU  - Raymond E
FAU - Faivre, Sandrine
AU  - Faivre S
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20120825
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - V99T50803M (Sunitinib)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Angiogenesis Inhibitors/therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Disease Progression
MH  - *Drug Resistance, Neoplasm
MH  - Etoposide/pharmacology
MH  - Everolimus
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Indoles/therapeutic use
MH  - Medical Oncology/methods
MH  - Neuroendocrine Tumors/*drug therapy
MH  - Pancreatic Neoplasms/*drug therapy
MH  - Pyrroles/therapeutic use
MH  - Sirolimus/analogs & derivatives/therapeutic use
MH  - Sunitinib
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2012/08/28 06:00
MHDA- 2013/03/08 06:00
CRDT- 2012/08/28 06:00
PHST- 2012/05/07 00:00 [received]
PHST- 2012/08/06 00:00 [accepted]
PHST- 2012/08/28 06:00 [entrez]
PHST- 2012/08/28 06:00 [pubmed]
PHST- 2013/03/08 06:00 [medline]
AID - 10.1007/s11523-012-0229-6 [doi]
PST - ppublish
SO  - Target Oncol. 2012 Sep;7(3):173-81. doi: 10.1007/s11523-012-0229-6. Epub 2012 Aug 
      25.