Targeted therapy in breast cancer: what's new?

L Fang,Z Barekati,Z Liu,Xy Zhong,B Zhang

doi:10.4414/smw.2011.13231

Abstract

Breast cancer is the most commonly diagnosed malignancy and one of the major causes of death among women. Breast cancer is also one of the most investigated diseases but whose biological features are still not well understood, several effective treating strategies having been explored in dealing with different types of advanced breast cancer, such as endocrine therapy and molecular targeted therapy. Trastuzumab is the first approved targeted anti-cancer agent to show an attractive response rate and outcomes in treating HER-2 positive metastatic breast cancer patients. However, primary or acquired trastuzumab resistance usually occurs some time into the use of trastuzumab and leads to treatment resistance or tumour progression. The promising results with trastuzumab targeted therapy encouraged further investigations in this area exploring several novel targeted agents aiming to overcome the resistance drawback of trastuzumab. In this review we discuss the major newly developed targeted agents in breast cancer treatment, including the novel anti-HER-2 monoclonal antibody pertuzumab or ertumaxomab, small molecular tyrosine inhibitor lapatinib, selective PARP1 inhibitor olaparib, mTOR inhibitor rapamycin analogues, and sheddase inhibitors. Many of these novel targeted drugs or molecules showed additional or complementary effects to trastuzumab therapy that need further and wider investigation.

Highlights

Breast cancer as a heterogeneous disease presents a wide range of pathological characteristics and clinical features
In March 2007, lapatinib was approved by the FDA as the first small molecular inhibitor targeting human epidermal growth factor receptor-2 (HER-2) for the treatment of patients with advanced or metastatic breast cancer based on a phase III, randomised trial of lapatinibcapecitabine combined regimen in patients with progressive, HER-2 positive, locally advanced/metastatic breast cancer as compared with capecitabine treatment alone [17]
This trial showed that the addition of lapatinib to capecitabine was associated with a 51% reduction in the risk of disease progression with no significant increase in toxic effect and less central nervous system (CNS) metastasis occurrence as compared with capecitabine monotherapy

Summary

Breast cancer is the most commonly diagnosed malignancy and one of the major causes of death among women. The promising results with trastuzumab targeted therapy encouraged further investigations in this area exploring several novel targeted agents aiming to overcome the resistance drawback of trastuzumab. In this review we discuss the major newly developed targeted agents in breast cancer treatment, including the novel anti-HER-2 monoclonal antibody pertuzumab or ertumaxomab, small molecular tyrosine inhibitor lapatinib, selective PARP1 inhibitor olaparib, mTOR inhibitor rapamycin analogues, and sheddase inhibitors. Many of these novel targeted drugs or molecules showed additional or complementary effects to trastuzumab therapy that need further and wider investigation

Introduction

Review article

Antiangiogenesis and VEGF inhibitors

ADAMs and selective ADAMs inhibitors

Findings

Conclusions