PMID- 21858654
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20220410
IS  - 1573-7403 (Electronic)
IS  - 1386-341X (Linking)
VI  - 15
IP  - 1
DP  - 2012 Mar
TI  - New targeted therapies in pituitary carcinoma resistant to temozolomide.
PG  - 37-43
LID - 10.1007/s11102-011-0341-0 [doi]
AB  - To evaluate the antitumoral efficacy of everolimus in pituitary carcinoma 
      resistant to temozolomide, the correlation with mammalian target of rapamycin 
      (mTOR) signaling in the tumor and to present recent advances and future 
      treatments of pituitary carcinomas. Pituitary carcinomas are rare and largely 
      unresponsive to current treatment options. Recent reports on the antitumoral 
      efficacy of temozolomide in some such patients are encouraging, yet most patients 
      appear to show resistance to its actions. As a potential alternative, the mTOR 
      inhibitor, everolimus, has been shown to potently inhibit pituitary cell 
      proliferation highlighting mTOR inhibition as a promising therapeutic approach 
      for pituitary carcinomas. We described the tumoral effects of a combination 
      therapy with everolimus (5 mg/day) and octreotide (30 mg/month) and the mTOR 
      signalling expression in a patient with pituitary ACTH carcinoma, compared to 17 
      other ACTH adenomas. Clinical and biochemical evaluation were performed every 
      month, and imaging after 3 month of treatment. mTOR signaling was assessed by 
      microarray expression analysis of each of the 18 adenoma tissues. Combined 
      therapy failed to control pituitary tumor growth and ACTH secretion. Slight 
      activation of mTOR signaling was found in all ACTH tumors alongside important 
      variations between tumors. Low antitumor efficacy shown by everolimus might be 
      explained by the weak activation of mTOR pathway in ACTH tumors. Everolimus 
      treatment was inefficient at controlling secretion and tumor growth of one ACTH 
      pituitary carcinoma. More clinical cases, with mTOR signalling expression 
      analysis of the tumor, must be published before any conclusions can be drawn.
FAU - Jouanneau, Emmanuel
AU  - Jouanneau E
AD  - INSERM, U1028/CNRS, UMR5292. Lyon Neuroscience Research Center, Neuro-Oncology 
      and Neuro-inflammation Team, 69000, Lyon, France.
FAU - Wierinckx, Anne
AU  - Wierinckx A
FAU - Ducray, Francois
AU  - Ducray F
FAU - Favrel, Veronique
AU  - Favrel V
FAU - Borson-Chazot, Francoise
AU  - Borson-Chazot F
FAU - Honnorat, Jerome
AU  - Honnorat J
FAU - Trouillas, Jacqueline
AU  - Trouillas J
FAU - Raverot, Gerald
AU  - Raverot G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pituitary
JT  - Pituitary
JID - 9814578
RN  - 7GR28W0FJI (Dacarbazine)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Dacarbazine/*analogs & derivatives/therapeutic use
MH  - Drug Resistance, Neoplasm
MH  - Everolimus
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pituitary Neoplasms/*drug therapy
MH  - Sirolimus/analogs & derivatives/therapeutic use
MH  - Temozolomide
EDAT- 2011/08/23 06:00
MHDA- 2012/07/17 06:00
CRDT- 2011/08/23 06:00
PHST- 2011/08/23 06:00 [entrez]
PHST- 2011/08/23 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
AID - 10.1007/s11102-011-0341-0 [doi]
PST - ppublish
SO  - Pituitary. 2012 Mar;15(1):37-43. doi: 10.1007/s11102-011-0341-0.