HER2-targeted Therapeutic Strategies for HER2-positive Metastatic Breast Cancers

Title:HER2-targeted Therapeutic Strategies for HER2-positive Metastatic Breast Cancers

Volume: 10 Issue: 3

Author(s): Teruhiko Fujii, Keisuke Miwa, Tomoyuki Ushijima, Mototsugu Matsunaga, Masaru Fukahori, Kotaro Yuge, Uhi Toh, Nobutaka Iwakuma, Ryuji Takahashi, Hiroki Takahashi, Miki Takenaka, Mai Mishima, Yoshito Akagi, Masayoshi Kage and Shino Nakagawa

Affiliation:

Keywords: Advanced breast cancer, human epidermal growth factor receptor (HER), metastatic breast cancer, molecularlytargeted therapy.

Abstract: The development of effective chemotherapy or endocrine therapy has significantly improved survival among patients with breast cancer, and recently molecular cancer therapeutics is emerging as another new approach. The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases is an attractive target for anticancer strategies. Trastuzumab is a humanized monoclonal antibody that binds directly to domain IV of the extracellular region of HER2, suppressing HER2 signaling activity, and marking tumor cells that overexpress HER2 for further immunological attack through antibody-dependent cellular cytotoxicity (ADCC). Trastuzumab is a key drug in the treatment strategy for HER2- positive breast cancer in neoadjuvant, adjuvant and metastatic diseases. However, a significant proportion of HER2- overexpressing breast cancer patients either do not respond or eventually become resistant to trastuzumab. For this reason, numerous new agents and therapeutic strategies are under investigation. Lapatinib is an oral small-molecule tyrosine kinase inhibitor (TKI) that reversibly and selectively inhibits both HER1 and HER2, and findings suggest that lapatinib is a potential therapeutic for breast cancer patients who are resistant to trastuzumab. Other agents, such as pertuzumab or TDM1, have shown promising results in clinical trials of breast cancer. Furthermore, strategies combining multiple HER2- targeted therapies might offer additive or synergic effects, and lead to improved outcomes. Here we describe the latest preclinical and clinical developments in HER2-targeting therapeutic strategies for breast cancer.

Cite this article as:

Fujii Teruhiko, Miwa Keisuke, Ushijima Tomoyuki, Matsunaga Mototsugu, Fukahori Masaru, Yuge Kotaro, Toh Uhi, Iwakuma Nobutaka, Takahashi Ryuji, Takahashi Hiroki, Takenaka Miki, Mishima Mai, Akagi Yoshito, Kage Masayoshi and Nakagawa Shino, HER2-targeted Therapeutic Strategies for HER2-positive Metastatic Breast Cancers, Current Cancer Therapy Reviews 2014; 10 (3) . https://dx.doi.org/10.2174/157339471003150212111019