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Hindawi Publishing Corporation

Journal of Oncology

Volume 2010, Article ID 149362, 11 pages

doi:10.1155/2010/149362

Review A rticle

A Current Review of Targeted Therapeutics for Ovar i an Cancer

Susana M. Campos

and Sue Ghosh

Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA

Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

Correspondence should be addressed to Susana M. Campos, [email protected]

Received 9 July 2009; Accepted 28 September 2009

Academic Editor: Maurie M. Markman

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly

cited.

Diﬃcult to detect, ovarian cancer typically presents at an advanced stage. Signiﬁcant progress has been achieved in the treatment

of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction

chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease oﬀer little in

terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These

include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal

antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the

vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the

management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP

inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

1. Introduction

Various targeted therapeutics have been explored in the

management of ovarian cancer. These include monoclonal

antibodies to Her 2 neu [1, 2] and other epidermal growth

factor receptors [3] (i.e., Trastuzumab [1], Pertuzumab

[2], and EMD 7200 [3]), small molecule tyrosine kinase

inhibitors that targeted the various EGFR receptors (geﬁtinib

[4], erlotinib [5], CI-1033 [6]), monoclonal antibodies

directed at the vascular endothelial growth factor [7–19]

(bevacizumab), and the small tyrosine kinase inhibitors

that target the vascular endothelial growth factor receptor

[20–25]. Recently, several other agents have come forth as

potential therapeutic agents in the management of ovarian

cancer. These include monoclonal antibodies to the folate

receptor, triple angiokinase inhibitors, PARP inhibitors,

aurora kinase inhibitors, inhibitors of the Hedgehog path-

way, folate receptor antagonists, and MTOR inhibitors.

This paper will explore the current data on the various

targeted approaches in ovarian cancer. Attention will be

directed at understanding the molecular mechanisms of

these agents balanced with their application to clinical

practice.

2. Angiogenesis

Enthusiasm for cytotoxic agents in the management of

ovarian cancer has been tempered by the emergence of

resistance. As such, a focus on alternative innovative thera-

peutics has emerged. One such direction is the inhibition of

angiogenesis. Angiogenesis is one of the cardinal processes

leading to invasion and metastasis of solid tumors. The

angiogenic-signaling pathway may be triggered by the release

of angiogenic ligands such as the vascular endothelial

growth factor from tumor cells. Tumor angiogenesis is well

established as essential for the growth and metastasis of solid

tumors, [26–28] This process involves the recruitment of

mature vasculature and circulating endothelial cells [29, 30]

and proangiogenic soluble mediators one of which includes

the vascular endothelial growth factor (VEGF) [31]. This

factor has several known activities [31], such as mitogenesis,

angiogenesis, endothelial survival, enhancement of vascular

permeability, and eﬀects on hemodynamic status. In ovarian

cancer increased levels of VEGF are associated with poor

prognosis and have been conﬁrmed in multivariate analysis

as an independent prognostic indicator of survival [28, 32–

38]. Given the poor long-term responses appreciated with

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