PMID- 19923318
OWN - NLM
STAT- MEDLINE
DCOM- 20100223
LR  - 20211203
IS  - 1535-2900 (Electronic)
IS  - 1079-2082 (Linking)
VI  - 66
IP  - 23 Suppl 6
DP  - 2009 Dec 1
TI  - Emerging treatment combinations: integrating therapy into clinical practice.
PG  - S9-S14
LID - 10.2146/ajhp090439 [doi]
AB  - PURPOSE: To review data supporting the effectiveness of emerging treatment 
      options for metastatic breast cancer. SUMMARY: Recent research has focused on 
      several signal-transduction pathways important in the pathogenesis of breast 
      cancer. Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase 
      that is involved in cell growth and survival. Everolimus, an orally active 
      inhibitor of mTOR, has demonstrated promising efficacy results and a favorable 
      safety profile in initial studies. Epidermal growth factor receptor (EGFR), a 
      cell-surface molecule that has been implicated in the pathogenesis of breast 
      cancer, may also be important in the emergence of resistance to endocrine 
      therapy. Initial clinical studies have suggested that EGFR inhibitors such as 
      gefitinib may delay the development of resistance to endocrine therapy in 
      patients with breast cancer when given concurrently with tamoxifen or an 
      aromatase inhibitor. Finally, considerable recent research has examined the role 
      of epigenetic gene silencing, in which acetylation or deacetylation of DNA 
      modifies the expression of tumor-suppressing genes. The enzyme histone 
      deacetylase (HDAC) suppresses gene transcription by modifying chromatin into a 
      more compact form. HDAC inhibitors have emerged as a potential new treatment 
      option for several cancer types, including breast cancer. The HDAC inhibitor 
      vorinostat has recently been examined in combination with other treatments, 
      including cytotoxic agents and bevacizumab, for the treatment of breast cancer. 
      In one small Phase I and II study, first-line treatment with the combination of 
      vorinostat, paclitaxel, and bevacizumab produced objective responses (partial or 
      complete) in more than 50% of patients with recurrent or metastatic breast 
      cancer. CONCLUSIONS: Although the results of the described studies are promising, 
      randomized controlled clinical trials are needed to better understand the 
      efficacy and safety of emerging treatment options for patients with metastatic 
      breast cancer.
FAU - Wong, Serena T
AU  - Wong ST
AD  - The Cancer Institute of New Jersey, University of Medicine and Dentistry of New 
      Jersey, New Brunswick, NJ 08903-2681, USA. wongse@umdnj.edu
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Am J Health Syst Pharm
JT  - American journal of health-system pharmacy : AJHP : official journal of the 
      American Society of Health-System Pharmacists
JID - 9503023
RN  - 0 (Drugs, Investigational)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Quinazolines)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - S65743JHBS (Gefitinib)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*drug therapy
MH  - Drug Delivery Systems
MH  - Drugs, Investigational/administration & dosage/pharmacology
MH  - ErbB Receptors/antagonists & inhibitors
MH  - Everolimus
MH  - Female
MH  - Gefitinib
MH  - Histone Deacetylase Inhibitors/administration & dosage
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/antagonists & inhibitors
MH  - Models, Biological
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors
MH  - Quinazolines/administration & dosage/pharmacology
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/administration & dosage/analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases
RF  - 24
EDAT- 2009/12/16 06:00
MHDA- 2010/02/24 06:00
CRDT- 2009/11/20 06:00
PHST- 2009/11/20 06:00 [entrez]
PHST- 2009/12/16 06:00 [pubmed]
PHST- 2010/02/24 06:00 [medline]
AID - 66/23_Supplement_6/S9 [pii]
AID - 10.2146/ajhp090439 [doi]
PST - ppublish
SO  - Am J Health Syst Pharm. 2009 Dec 1;66(23 Suppl 6):S9-S14. doi: 
      10.2146/ajhp090439.