7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Neuro-ophthalmic side effects of molecularly targeted cancer drugs

      ,
      Eye
      Springer Nature

      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

          <p class="first" id="d1265523e168">The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity. The United States Food and Drug Administration approval of the chimeric monoclonal antibody (mAb) rituximab in 1997 for the treatment of B cell non-Hodgkin lymphoma ushered in a new era of targeted therapy for cancer. A year later, trastuzumab, a humanized mAb, was approved for patients with breast cancer. In 2001, imatinib was the first small-molecule kinase inhibitor approved. The approval of ipilimumab—the first in class immune checkpoint inhibitor—in 2011 serves as a landmark period of time in the resurgence of immunotherapy for cancer. Despite the notion that increased tumor specificity results in decreased complications, toxicity remains a major hurdle in the development and implementation of many of the targeted anticancer drugs. This article will provide an overview of the current cellular and immunological understanding of cancer pathogenesis—the foundation upon which molecularly targeted therapies were developed—and a description of the ocular and neuro-ophthalmic toxicity profile of mAbs, immune checkpoint inhibitors, and small-molecule kinase inhibitors. </p>

          Related collections

          Most cited references67

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

          Antibody targeted drugs as cancer therapeutics.

          Treatment of cancer is a double-edged sword: it should be as aggressive as possible to completely destroy the tumour, but it is precisely this aggressiveness which often causes severe side effects - a reason why some promising therapeutics can not be applied systemically. In addition, therapeutics such as cytokines that physiologically function in a para- or autocrine fashion require a locally enhanced level to exert their effect appropriately. An elegant way to accumulate therapeutic agents at the tumour site is their conjugation/fusion to tumour-specific antibodies. Here, we discuss recent preclinical and clinical data for antibody-drug conjugates and fusion proteins with a special focus on drug components that exert their antitumour effects through normal biological processes.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The clinical development of MEK inhibitors.

            Aberrant activation of the RAS-RAF-MEK-ERK1/2 pathway occurs in more than 30% of human cancers. As part of this pathway, MEK1 and MEK2 have crucial roles in tumorigenesis, cell proliferation and inhibition of apoptosis and, therefore, MEK1/2 inhibition is an attractive therapeutic strategy in a number of cancers. Highly selective and potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed and assessed in numerous clinical studies over the past decade. These agents are not efficacious in a broad range of unselected cancers, although single-agent antitumour activity has been detected mainly in tumours that harbour mutations in genes encoding the members of the RAS and RAF protein families, such as certain melanomas. Combinations of MEK1/2 inhibitors and cytotoxic chemotherapy, and/or other targeted agents are being studied to expand the efficacy of this class of agents. Identifying predictive biomarkers, and delineating de novo and acquired resistance mechanisms are essential for the future clinical development of MEK inhibitors. We discuss the clinical experience with MEK inhibitors to date, and consider the novel approaches to MEK-inhibitor therapy that might improve outcomes and lead to the wider use of such treatments.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer.

              Paraneoplastic encephalitides usually precede a diagnosis of cancer and are often refractory to immunosuppressive therapy. Conversely, autoimmune encephalitides are reversible conditions that can occur in the presence or absence of cancer.
                Bookmark

                Author and article information

                Journal
                Eye
                Eye
                Springer Nature
                0950-222X
                1476-5454
                October 20 2017
                October 20 2017
                :
                :
                Article
                10.1038/eye.2017.222
                5811730
                29052609
                61a8394f-9047-4ec8-8fdd-527ddd373ac8
                © 2017
                History

                Comments

                Comment on this article