Recent advances in novel targeted therapies for HER2-positive breast cancer Journal Article
| Authors: | Murphy, C. G.; Morris, P. G. |
| Article Title: | Recent advances in novel targeted therapies for HER2-positive breast cancer |
| Abstract: | The monoclonal antibody trastuzumab has improved the outcomes of patients with breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2). However, despite this advancement, many tumors develop resistance and novel approaches are needed. Recently, a greater understanding of cellular biology has translated into the development of novel anti-HER2 agents with varying mechanisms of action. The small molecule tyrosine kinase inhibitor lapatinib has demonstrated activity in HER2-positive metastatic breast cancer (MBC) and in the preoperative setting. Pertuzumab is a monoclonal antibody with a distinct binding site from trastuzumab, which inhibits receptor dimerization. In recent studies, the addition of pertuzumab to combination therapy has led to improvements in progression-free survival in patients with HER2-positive MBC and higher response rates in the preoperative setting. An alternative approach is the use of novel antibody-drug conjugates such as trastuzumab-emtansine, which recently demonstrated activity in MBC. Neratinib, a pan-HER tyrosine kinase inhibitor, which irreversibly inhibits HER1 and HER2, also has proven activity in MBC. A range of compounds is being developed to attempt to overcome trastuzumab resistance by targeting heat shock protein 90, a molecular chaperone required for the stabilization of cellular proteins. Furthermore, agents are being developed to inhibit the mammalian target of rapamycin, a downstream component of the PTEN/PI3K pathway, which has been implicated in trastuzumab resistance. Finally, there are emerging data indicating that combinations of anti-HER2 agents may circumvent resistance mechanisms and improve patient outcomes. In this review, recent data on these emerging agents and novel combinations for HER2-positive breast cancer are discussed. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. |
| Keywords: | signal transduction; protein kinase b; cancer survival; treatment outcome; review; cancer combination chemotherapy; diarrhea; nonhuman; antineoplastic agents; drug targeting; paclitaxel; antineoplastic agent; animals; cell cycle; epidermal growth factor receptor 2; drug resistance, neoplasm; drug design; breast neoplasms; phosphatidylinositol 3 kinase; docetaxel; febrile neutropenia; cancer inhibition; drug mechanism; add on therapy; cardiotoxicity; mammalian target of rapamycin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; tanespimycin; heat shock protein 90; binding site; receptor, erbb-2; trastuzumab; anthracycline; breast metastasis; everolimus; lapatinib; drug binding; neratinib; pertuzumab; chaperone; phase 3 clinical trial (topic); molecular targeted therapy; trastuzumab resistance; trastuzumab emtansine; estrogen receptor positive breast cancer; brentuximab vedotin; antibody-drug conjugates; novel anti-her2 therapy; trastuzumab-emtansine |
| Journal Title: | Anti-Cancer Drugs |
| Volume: | 23 |
| Issue: | 8 |
| ISSN: | 0959-4973 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2012-09-01 |
| Start Page: | 765 |
| End Page: | 776 |
| Language: | English |
| DOI: | 10.1097/CAD.0b013e328352d292 |
| PROVIDER: | scopus |
| PUBMED: | 22824822 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: ANTDE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work