title: Modulation of the immune response and tumor growth by activated Ras.
abstract: As a result of its transforming abilities, activated Ras is expressed in a great number of cancers. The ras mutation frequency varies between 95% in pancreatic cancer and 5% in breast cancer. In leukemia, the highest frequency (30%) is found in acute myeloid leukemia. The presence of ras mutations has been correlated with a poor prognosis and negative clinical outcome. This suggests that mutated Ras activates mechanisms, which favor tumor growth, enhance the metastatic capacity of tumors or modulate tumor-specific immune responses. Several new functions of Ras, such as downregulation of major histocompatibility complex molecules, upregulation of certain cytokines, growth factors and degradative enzymes have been uncovered in the last decade. Additionally, mutated Ras can also serve as a primary target for the development of immunotherapy or drug therapy. This review will discuss the mechanisms by which Ras expressing tumors are able to evade destruction by the immune system and enhance their growth and metastatic potential. It will further elaborate on the attempts to develop successful immunotherapy and drug therapy targeting Ras expressing tumors.
authors.affiliation: Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: S
authors.initials: S
authors.lastname: Weijzen
authors.forename: M P
authors.initials: MP
authors.lastname: Velders
authors.forename: W M
authors.initials: WM
authors.lastname: Kast
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D017951:Antigen Presentation; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D051231:Farnesyltranstransferase; D005656:Fungal Proteins / Q000502:physiology; D016044:Fusion Proteins, bcr-abl / Q000502:physiology; D011905:Genes, ras; D006133:Growth Substances / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D007167:Immunotherapy; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D025542:Neurofibromin 1; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011506:Proteins / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors / Q000502:physiology*; D012088:Reoviridae Infections / Q000503:physiopathology; D012097:Repressor Proteins / Q000502:physiology; D020837:SOS1 Protein; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005656:Fungal Proteins; D006133:Growth Substances; D009363:Neoplasm Proteins; D025542:Neurofibromin 1; D016376:Oligonucleotides, Antisense; D011506:Proteins; D012097:Repressor Proteins; D020837:SOS1 Protein; D006160:Guanosine Triphosphate; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D016044:Fusion Proteins, bcr-abl; D010450:Endopeptidases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)