Table of Contents
ISRN Oncology
Volume 2011, Article ID 403098, 13 pages
http://dx.doi.org/10.5402/2011/403098
Review Article

Pathway Profiling and Rational Trial Design for Studies in Advanced Stage Cervical Carcinoma: A Review and a Perspective

1Département d’Oncologie, Institut Curie, 75005 Paris, France
2Centrum Gynaecologische Oncologie Amsterdam, AMC, NKI-AVL, and VUmc, 1007 MB, Amsterdam, The Netherlands
3Department of Gynacologic Oncology & Gynaecology, University Hospital of Essen, Henricistrasse 92, 45136 Essen, Germany

Received 4 April 2011; Accepted 30 April 2011

Academic Editors: A. Goussia, H.-W. Lo, and S. Mohanam

Copyright © 2011 Susy M. E. Scholl et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment.