Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer

• Type of Material: Article
• Authors: Anna E. Kersh, Emory University; Spencer Ng, Emory University; Yun Min Chang, Emory University; Maiko Sasaki, Atlanta VA Medical Center; Susan N. Thomas, Emory University; Haydn Kissick, Emory University; Gregory Lesinski, Emory University; Ragini Kudchadkar, Emory University; Edmund Waller, Emory University; Brian Pollack, Emory University
• Language: English
• Date: 2018-01-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, The American College of Clinical Pharmacology
• Final Published Version (URL): http://dx.doi.org/10.1002/jcph.1028
• Title of Journal or Parent Work: Journal of Clinical Pharmacology
• ISSN: 0091-2700
• Volume: 58
• Issue: 1
• Start Page: 7
• End Page: 24
• Grant/Funding Information: E. K.W. is supported by NIH Grant R01CA74364.; B.P.P. is supported by a Merit Review Award (5I01BX001922) from the Department of Veterans Affairs, a Career Development Award from the Melanoma Research Foundation, funding from the Skin Cancer and Melanoma Fund of the Winship Cancer Institute, and the Melanoma Innovation Fund of the Winship Cancer Institute.; G.B.L. is supported by NIH Grant R01CA208253-01.; H.K. is supported by NIH grant K99CA197801.; S.N.T. is supported by National Institutes of Health (NIH) Grant R01CA207619 and Department of Defense Grant CA150523.; A.E.K., S.N., and Y.M.C. are supported by the Medical Scientist Training Program at Emory University School of Medicine.
• Keywords: ANTIGEN-PROCESSING PATHWAY; MHC CLASS-I; Immunopharmacology; Oncology; ACUTE MYELOGENOUS LEUKEMIA; Pharmacology & Pharmacy; TYROSINE KINASE INHIBITOR; Science & Technology; Life Sciences & Biomedicine; RENAL-CELL CARCINOMA; MONOCLONAL-ANTIBODY THERAPY; FACTOR RECEPTOR ANTIBODIES; INDUCED IMMUNE SUPPRESSION; METASTATIC BREAST-CANCER; EPIDERMAL-GROWTH-FACTOR; Molecular Biology; Pharmaceutical R & D; Drug Information
• Research Categories: Biology, Microbiology; Health Sciences, Pharmacology; Health Sciences, Oncology

Abstract

Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as “targeted therapies”) and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor-immune microenvironment. Although these 2 modalities were developed and initially used independently, combination regimens are now being tested in clinical trials, underscoring the need to understand how targeted therapies influence immunologic events. Translational studies and preclinical models have demonstrated that targeted therapies can influence immune cell trafficking, the production of and response to chemokines and cytokines, antigen presentation, and other processes relevant to antitumor immunity and immune homeostasis. Moreover, because these and other effects of targeted therapies occur in nonmalignant cells, targeted therapies are being evaluated for use in applications outside of oncology.