Cancer. 2008 Feb 1;112(3 Suppl):710-7.

Enhancing endocrine response with novel targeted therapies: why have the clinical trials to date failed to deliver on the preclinical promise?

Johnston SR, Leary A, Martin LA, Smith IE, Dowsett M.

Source

Department of Medicine, Royal Marsden Hospital, Fulham Road, Chelsea, London, UK.

Abstract

Acquired resistance to endocrine therapies has severely limited their long-term effectiveness in breast cancer. In recent years a clear rationale has developed for combining signal transduction inhibitors (STIs) with endocrine therapies to delay the emergence of acquired resistance and enhance endocrine responsiveness. A variety of biologic agents have been developed to target key proteins along the EGFR, HER2, MAPK, and P13K/Akt signal transduction cascades. While several of these agents have shown early promise in selected breast cancer models, translating these data into convincing clinical results has been generally disappointing to date. By applying more rigorous trial design and tumor selection criteria to future trials, it is much more likely that adding the new generation of targeted therapies can fulfill its promise in enhancing endocrine responsiveness and our ability to treat breast cancer patients.

PMID:: 18072235; [PubMed - indexed for MEDLINE]

Free full text

MeSH Terms, Substances

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Breast Cancer - MedlinePlus Health Information

Supplemental Content

Save items

Related citations in PubMed

Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer. [Breast Cancer Res. 2007]
Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer.
Leary AF, Sirohi B, Johnston SR. Breast Cancer Res. 2007; 9(5):112.
Review Clinical strategies for rationale combinations of aromatase inhibitors with novel therapies for breast cancer. [J Steroid Biochem Mol Biol. 2007]
Review Clinical strategies for rationale combinations of aromatase inhibitors with novel therapies for breast cancer.
Johnston SR, Martin LA, Leary A, Head J, Dowsett M. J Steroid Biochem Mol Biol. 2007 Aug-Sep; 106(1-5):180-6. Epub 2007 May 24.
Review Clinical trials of intracellular signal transductions inhibitors for breast cancer--a strategy to overcome endocrine resistance. [Endocr Relat Cancer. 2005]
Review Clinical trials of intracellular signal transductions inhibitors for breast cancer--a strategy to overcome endocrine resistance.
Johnston SR. Endocr Relat Cancer. 2005 Jul; 12 Suppl 1:S145-57.
Endocrine and targeted manipulation of breast cancer: summary statement for the Sixth Cambridge Conference. [Cancer. 2008]
Endocrine and targeted manipulation of breast cancer: summary statement for the Sixth Cambridge Conference.
Come SE, Buzdar AU, Ingle JN, Johnston SR, Brodie AM, Coombes RC, Miller WR, Pritchard KI, Winer EP, Zujewski JA, et al. Cancer. 2008 Feb 1; 112(3 Suppl):673-8.
Review Enhancing the efficacy of hormonal agents with selected targeted agents. [Clin Breast Cancer. 2009]
Review Enhancing the efficacy of hormonal agents with selected targeted agents.
Johnston SR. Clin Breast Cancer. 2009 Jun; 9 Suppl 1:S28-36.

See reviews... See all...

Cited by 2 PubMed Central articles

Multiple roles and therapeutic implications of Akt signaling in cancer. [Onco Targets Ther. 2009]
Multiple roles and therapeutic implications of Akt signaling in cancer.
Calvo E, Bolós V, Grande E. Onco Targets Ther. 2009 Feb 18; 2:135-50. Epub 2009 Feb 18.
Integration of endocrine therapy with targeted agents. [Breast Cancer Res. 2008]
Integration of endocrine therapy with targeted agents.
Johnston SR. Breast Cancer Res. 2008; 10 Suppl 4:S20. Epub 2008 Dec 18.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Enhancing endocrine response with novel targeted therapies: why have the clinica...
Enhancing endocrine response with novel targeted therapies: why have the clinical trials to date failed to deliver on the preclinical promise?
Cancer. 2008 Feb 1 ;112(3 Suppl):710-7.

PubMed
Primary intracerebral and subarachnoid hemorrhage. An approach to diagnosis and ...
Primary intracerebral and subarachnoid hemorrhage. An approach to diagnosis and therapy.
Arq Neuropsiquiatr. 1991 Sep ;49(3):233-42.

PubMed
Assembly of the inner kinetochore proteins CENP-A and CENP-B in living human cel...
Assembly of the inner kinetochore proteins CENP-A and CENP-B in living human cells.
Chembiochem. 2008 Jan 4 ;9(1):77-92.

PubMed
Atherosclerosis and oxidative stress.
Atherosclerosis and oxidative stress.
Histol Histopathol. 2008 Mar ;23(3):381-90.

PubMed
IgG antibodies against food antigens are correlated with inflammation and intima...
IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles.
Exp Clin Endocrinol Diabetes. 2008 Apr ;116(4):241-5. Epub 2007 Dec 10 .

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: