For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
106
references
 Top references
cited by
12
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      510
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Human epidermal growth factor receptor targeted inhibitors for the treatment of ovarian cancer

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors (especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients, especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors. They have demonstrated valuable antitumor activity in multiple cancers and their possible use in ovarian cancer continues to be studied. In this review, we discuss the human epidermal growth factor receptor family; review emerging clinical studies on monoclonal antibodies and tyrosine kinase inhibitors targeting these receptors in ovarian cancer patients; and propose future research possibilities in this area.

          Related collections

          Most cited references106

          • Record: found
          • Abstract: found
          • Article: not found

          ErbB receptors and signaling pathways in cancer.

          Nancy E. Hynes, Gwen MacDonald (2009)
          The ErbB receptor tyrosine kinases play important roles in normal physiology and in cancer. Epidermal growth factor receptor (EGFR) and ErbB2 in particular are mutated in many epithelial tumors, and clinical studies suggest that they play roles in cancer development and progression. These receptors have been intensely studied, not only to understand the mechanisms underlying their oncogenic potential, but also to exploit them as therapeutic targets. ErbB receptors activate a multiplicity of intracellular pathways via their ability to interact with numerous signal transducers. Furthermore, there are now many ErbB-targeted inhibitors used in the clinic. In this review we will concentrate on breast tumors with ERBB2 gene amplification/receptor overexpression and non-small cell lung cancer (NSCLC) with activating EGFR mutations. We will discuss data showing the important role that the PI3K/Akt pathway plays, not only in cancer development, but also in response to targeted therapies. Finally, mechanisms contributing to resistance to ErbB-targeted therapeutics will also be discussed.
          Article 0 comments Cited 288 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

            Aman Buzdar, Nuhad K Ibrahim, Deborah Francis … (2005)
            The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.
            Article 0 comments Cited 234 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Role of tyrosine kinase inhibitors in cancer therapy.

              Amit Arora, Eric M Scholar (2005)
              Cancer chemotherapy has been one of the major medical advances in the last few decades. However, the drugs used for this therapy have a narrow therapeutic index, and often the responses produced are only just palliative as well as unpredictable. In contrast, targeted therapy that has been introduced in recent years is directed against cancer-specific molecules and signaling pathways and thus has more limited nonspecific toxicities. Tyrosine kinases are an especially important target because they play an important role in the modulation of growth factor signaling. This review focuses on small molecule inhibitors of tyrosine kinase. They compete with the ATP binding site of the catalytic domain of several oncogenic tyrosine kinases. They are orally active, small molecules that have a favorable safety profile and can be easily combined with other forms of chemotherapy or radiation therapy. Several tyrosine kinase inhibitors (TKIs) have been found to have effective antitumor activity and have been approved or are in clinical trials. The inhibitors discussed in this manuscript are imatinib mesylate (STI571; Gleevec), gefitinib (Iressa), erlotinib (OSI-1774; Tarceva), lapatinib (GW-572016), canertinib (CI-1033), semaxinib (SU5416), vatalanib (PTK787/ZK222584), sorafenib (BAY 43-9006), sutent (SU11248), and leflunomide (SU101). TKIs are thus an important new class of targeted therapy that interfere with specific cell signaling pathways and thus allow target-specific therapy for selected malignancies. The pharmacological properties and anticancer activities of these inhibitors are discussed in this review. Use of these targeted therapies is not without limitations such as the development of resistance and the lack of tumor response in the general population. The availability of newer inhibitors and improved patient selection will help overcome these problems in the future.
              Article 0 comments Cited 233 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Simon Peter Langdon
                Journal
                Journal ID (nlm-ta): Cancer Biol Med
                Journal ID (iso-abbrev): Cancer Biol Med
                Journal ID (publisher-id): CBM
                Title: Cancer Biology & Medicine
                Publisher: Chinese Anti-Cancer Association (Tianjing China )
                ISSN (Print): 2095-3941
                Publication date (Print): November 2018
                Volume: 15
                Issue: 4
                Pages: 375-388
                Affiliations
                [1] Cancer Research UK Edinburgh Center and Division of Pathology Laboratory, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
                Author notes
                Simon Peter Langdon, E-mail: simon.langdon@ 123456ed.ac.uk
                Article
                Publisher ID: cbm-15-4-375
                DOI: 10.20892/j.issn.2095-3941.2018.0062
                PMC ID: 6372909
                PubMed ID: 30766749
                SO-VID: 68f51e29-3a8d-48b0-9b96-3ea0192b65f5
                Copyright © Copyright 2017 Cancer Biology & Medicine
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                Date received : 6 April 2018
                Date accepted : 26 October 2018
                Categories
                Subject: Review

                Keywords: tyrosine kinase,monoclonal antibodies,ovarian cancer,inhibitors,her,receptors
                Data availability:
                Keywords: tyrosine kinase, monoclonal antibodies, ovarian cancer, inhibitors, her, receptors

                Comments

                Comment on this article

                scite_

                Similar content510

                See all similar

                Cited by12

                See all cited by

                Most referenced authors2,981

                See all reference authors