title: Combining targeted therapy with immunotherapy. Can 1+1 equal more than 2?
abstract: Targeted therapies have induced high response rates and improved survival in patients with cancer. However, the long-term effectiveness of targeted therapies has been limited by the development of acquired resistance in the majority of patients. On the other hand, the modern immunotherapy strategies have been associated with durable responses but in limited number of patients. Accordingly, research efforts have been focused on examining the effects of combinations of targeted therapy and immunotherapy in several different histological subtypes of cancer. There has been accumulated evidence to suggest that targeted therapy can induce immune effects in the tumor cells, the host immune system, and the tumor microenvironment. Subsequently, clinical trials have been designed to examine the efficacy of combining immune checkpoint blockade or adoptive cell transfer with tyrosine kinase inhibitors, HER family blockade, anti-angiogenic agents, histone deacetylase inhibitors, and cancer stem cell inhibitors. To date, the combination of immunotherapy with targeted therapy has demonstrated potential as a cancer treatment strategy, but further optimizations are required and caution must be taken to avoid toxicity. The current review summarizes existing evidence and provides rationale supporting the use of combined targeted and immune-therapy approaches in patients with different types of cancer.
authors: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
authors: Lidia
authors: L
authors: Robert
authors: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Surgery, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA; Department of Medical and Molecular Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center (JCCC) at UCLA, Los Angeles, CA 90095, USA.
authors: Antoni
authors: A
authors: Ribas
authors: Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center (JCCC) at UCLA, Los Angeles, CA 90095, USA. Electronic address: SHu-Lieskovan@mednet.ucla.edu.
authors: Siwen
authors: S
authors: Hu-Lieskovan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D056572:Histone Deacetylase Inhibitors; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Adoptive cell transfer; Combination therapy; Immune checkpoint blockade; Targeted therapy