Breast Cancer

, Volume 15, Issue 1, pp 49–56

Development of new targeted therapies for breast cancer

Conference Paper Symposium: Molecular target therapy

DOI: 10.1007/s12282-007-0003-2

Cite this article as:
Doyle, D.M. & Miller, K.D. Breast Cancer (2008) 15: 49. doi:10.1007/s12282-007-0003-2

Abstract

Clinical application of truly targeted therapy relies on identification of a specific molecular feature (the target) that is biologically relevant, reproducibly measurable and definably correlated with clinical benefit. Ideally the target should be crucial to the tumor’s malignant phenotype. The target must be easily measurable in readily obtained clinical samples. Interruption, interference or inhibition of the target should yield a clinical response in a significant proportion of patients whose tumors express the target but in few patients whose tumors do not express the target. As such, targeted therapy offers the twin hopes of maximizing efficacy while minimizing toxicity. A critical review of the hallmarks of malignancy provides a framework for considering potential targets and novel therapeutic interventions. The hallmarks of malignancy include uncontrolled proliferation, insensitivity to negative growth regulation, evasion of apoptosis, lack of senescence, invasion and metastasis, angiogenesis, and genomic elasticity. Existing therapies predominantly target proliferation either with cytotoxic agents, ionizing radiation or inhibition of estrogen receptor and HER2 growth factor signaling pathways. Further improvements in therapy must attack the other hallmarks of malignancy and will undoubtedly be accompanied by better means of individual patient selection for such therapies. Indeed, each of these hallmarks presents a therapeutic opportunity. To believe otherwise would be to assume that a feature is both biologically crucial yet therapeutically unimportant, an unlikely paradox.

Keywords

AngiogenesisMetastasisGrowth factorBevacizumabTrastuzumab

Copyright information

© The Japanese Breast Cancer Society 2007

Authors and Affiliations

  1. 1.Indiana University School of Medicine IndianapolisUSA
  2. 2.Indiana Cancer PavilionIndianapolisUSA