Why do so many cancer patients fail to respond to interferon therapy?

Since their first use in the clinic some 25 years ago, interferons (IFNs) have become accepted therapy in a range of cancer forms. However, although in some patients they induce remission, in the great majority they are of no benefit or, at best, lead only to minor improvements. This review considers possible reasons for these failures.

[1]  S. Bohlander,et al.  Nomenclature of the human interferon genes. , 1993, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[2]  D. Grandér,et al.  Response to interferon therapy in patients with multiple myeloma correlates with expression of the Bcl‐2 oncoprotein , 1995, International journal of cancer.

[3]  A. Kimchi,et al.  Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death. , 1995, Genes & development.

[4]  L. Hartwell,et al.  Cell cycle control and cancer. , 1994, Science.

[5]  D. Bosco,et al.  Interferon-γ (IFN-γ) Induces Programmed Cell Death in Differentiated Human Leukemic B Cell Lines , 1994 .

[6]  K. Öberg.  Treatment of neuroendocrine tumors. , 1994, Cancer treatment reviews.

[7]  B. Millar,et al.  Neutralising antibodies in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b. , 1994, British Journal of Cancer.

[8]  D. Grandér,et al.  Primary leukemia cells resistant to alpha-interferon in vitro are defective in the activation of the DNA-binding factor interferon- stimulated gene factor 3 , 1994 .

[9]  T. Taniguchi,et al.  Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1 , 1994, Cell.

[10]  J. Darnell,et al.  Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. , 1994, Science.

[11]  A. Wilks,et al.  JAK protein tyrosine kinases: their role in cytokine signalling. , 1994, Trends in cell biology.

[12]  F. Belardelli,et al.  Interaction of IFN α/β with host cells essential to the early inhibition of friend erythroleukemia visceral metastases in mice , 1994 .

[13]  J. Marx.  New tumor suppressor may rival p53. , 1994, Science.

[14]  K. Shuai,et al.  Interferon-activated signal transduction to the nucleus. , 1994, Current opinion in cell biology.

[15]  D. Grandér,et al.  Interferon system defects in malignant T-cells. , 1994, Leukemia.

[16]  J U Gutterman,et al.  Cytokine therapeutics: lessons from interferon alpha. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[17]  E. Petricoin,et al.  Human cancer cell lines express a negative transcriptional regulator of the interferon regulatory factor family of DNA binding proteins. , 1994, Molecular and cellular biology.

[18]  J. Marx.  How cells cycle toward cancer. , 1994, Science.

[19]  C. Gregory,et al.  Apoptosis in Burkitt lymphoma cells is driven by c-myc. , 1993, Oncogene.

[20]  T. Hunter.  Cytokine connections , 1993, Nature.

[21]  J. Stevens,et al.  Inhibitory Effects of α-Interferon on Epidermal Growth Factor-mediated Receptor-dependent Events , 1993 .

[22]  A. Kimchi,et al.  Interferons and interleukin-6 suppress the DNA-binding activity of E2F in growth-sensitive hematopoietic cells , 1993, Molecular and cellular biology.

[23]  K. Ozato,et al.  Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription , 1993, Molecular and cellular biology.

[24]  K. Öberg,et al.  An update of the medical treatment of malignant endocrine pancreatic tumors. , 1993, Acta oncologica.

[25]  D. Grandér,et al.  Cytotoxic effect of interferon on primary malignant tumour cells. Studies in various malignancies. , 1993, European journal of cancer.

[26]  M. Katze,et al.  Tumor suppressor function of the interferon-induced double-stranded RNA-activated protein kinase. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Åman,et al.  The EBNA2-related resistance towards alpha interferon (IFN-alpha) in Burkitt's lymphoma cells effects induction of IFN-induced genes but not the activation of transcription factor ISGF-3 , 1992, Molecular and cellular biology.

[28]  A. Kimchi.  Cytokine triggered molecular pathways that control cell cycle arrest , 1992, Journal of cellular biochemistry.

[29]  L. Thurmond,et al.  Antibodies in patients with recurrent respiratory papillomatosis treated with lymphoblastoid interferon. , 1991, The Journal of laboratory and clinical medicine.

[30]  T. Haferlach,et al.  Effective natural interferon-alpha therapy in recombinant interferon-alpha-resistant patients with hairy cell leukemia. , 1991, Blood.

[31]  H. Hochkeppel,et al.  Treatment of anti‐recombinant interferon‐alpha 2 antibody positive CML patients with natural interferon‐alpha , 1991, British journal of haematology.

[32]  H. Thomas,et al.  Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[33]  O. Turriziani,et al.  Neutralizing Antibodies to Interferon-α: Relative Frequency in Patients Treated with Different Interferon Preparations , 1991, The Journal of infectious diseases.

[34]  C. Zent,et al.  Treatment options for hairy-cell leukemia. , 1991, Seminars in oncology.

[35]  W. Wilmanns,et al.  Donor Leukocyte Transfusions for Treatment of Recurrent Chronic Myelogenous Leukemia in Marrow Transplant Patients , 1990 .

[36]  T. Taniguchi,et al.  Absence of the type I IFN system in EC cells: Transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated , 1990, Cell.

[37]  P. Giomarelli,et al.  Interferon levels in human pulmonary tumors are lower than plasma levels. , 1990, Journal of biological regulators and homeostatic agents.

[38]  C. Billard,et al.  In vivo and in vitro induction of 2'-5' oligoadenylate synthetase by interferon-alpha in nodular non-Hodgkin's lymphoma and correlations with the clinical response. , 1990, Journal of biological regulators and homeostatic agents.

[39]  D. Grandér,et al.  Interferon-induced enhancement of 2',5'-oligoadenylate synthetase in mid-gut carcinoid tumours , 1990, The Lancet.

[40]  E. Proietti,et al.  Inhibition by Mouse α/β-Interferon of the Multiplication of α/β-Interferon-resistant Friend Erythroleukemia Cells Cocultured with Mouse Hepatocytes , 1990 .

[41]  D. D. Hoff,et al.  He's not going to talk about in vitro predictive assays again, is he? , 1990, Journal of the National Cancer Institute.

[42]  C W White,et al.  Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. , 1989, The New England journal of medicine.

[43]  H. Dvorak,et al.  Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. , 1989, Journal of the National Cancer Institute.

[44]  D. Levy,et al.  Cells resistant to interferon are defective in activation of a promoter‐binding factor. , 1988, The EMBO journal.

[45]  M. Baseler,et al.  ANTI-RETROVIRAL EFFECTS OF INTERFERON-α IN AIDS-ASSOCIATED KAPOSI'S SARCOMA , 1988, The Lancet.

[46]  F. Grignani,et al.  Interferon alpha-2b as therapy for Ph'-positive chronic myelogenous leukemia: a study of 82 patients treated with intermittent or daily administration. , 1988, Blood.

[47]  D. Longo,et al.  Resistance to recombinant interferon alfa-2a in hairy-cell leukemia associated with neutralizing anti-interferon antibodies. , 1988, The New England journal of medicine.

[48]  J. Darnell,et al.  Transcription of interferon-stimulated genes is induced by adenovirus particles but is suppressed by E1A gene products , 1988, Journal of virology.

[49]  A. van den Hooff,et al.  Stromal involvement in malignant growth. , 1988 .

[50]  D. Grandér,et al.  Induction of 2',5'-oligoadenylate synthetase in freshly separated malignant cells from solid tumors. Variability in the susceptibility of interferon. , 1987, European journal of cancer & clinical oncology.

[51]  M. Rosenblum,et al.  Clinical and laboratory changes induced by alpha interferon in chronic lymphocytic leukemia‐a pilot study , 1987, American journal of hematology.

[52]  J. Gutterman,et al.  In vivo sensitivity and resistance of chronic myelogenous leukemia cells to alpha-interferon: correlation with receptor binding and induction of 2',5'-oligoadenylate synthetase. , 1986, Cancer research.

[53]  Michael Loran Dustin,et al.  Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). , 1986, Journal of immunology.

[54]  D. Faller,et al.  Interferon-gamma induction of LFA-1-mediated homotypic adhesion of human monocytes. , 1986, Journal of immunology.

[55]  G. Juliusson,et al.  Chronic B-lymphocytic leukemia cells proliferate and differentiate following exposure to interferon in vitro. , 1986, Blood.

[56]  K. Nilsson,et al.  Correlation between in vitro and in vivo sensitivity to human leucocyte interferon in patients with multiple myeloma. , 2009, Scandinavian journal of haematology.

[57]  A. Kimchi,et al.  Inhibitory effects of interferon on the expression of genes regulated by platelet-derived growth factor. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Samuel J. Taylor,et al.  A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial. , 1985, Cancer research.

[59]  J. Vilček,et al.  Cytolytic activity of interferon‐gamma and its synergism with 5‐fluorouracil , 1984, International journal of cancer.

[60]  M. Dron,et al.  Isolation of Daudi cells with reduced sensitivity to interferon. I. Characterization. , 1983, The Journal of general virology.

[61]  E. Fish,et al.  Human leukocyte interferon subtypes have different antiproliferative and antiviral activities on human cells. , 1983, Biochemical and biophysical research communications.

[62]  H. Strander,et al.  Interferon and natural killer activity in multiple myeloma. Lack of correlation between interferon‐induced enhancement of natural killer activity and clinical response to human interferon‐α , 1982, International journal of cancer.

[63]  M. Hokland,et al.  Enhanced expression of beta2-microglobulin and HLA antigens on human lymphoid cells by interferon. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[64]  L. Sachs.  Control of normal cell differentiation and the phenotypic reversion of malignancy in myeloid leukaemia , 1978, Nature.

[65]  D. Burke,et al.  Appearance of interferon inducibility and sensitivity during differentiation of murine teratocarcinoma cells in vitro , 1978, Cell.

[66]  H. Strander,et al.  Is interferon tissue specific?- Effect of human leukocyte and fibroblast interferons on the growth of lymphoblastoid and osteosarcoma cell lines. , 1977, The Journal of general virology.

[67]  K. Cantell,et al.  Circulating human interferon after intramuscular injection into animals and man. , 1974, The Journal of general virology.

[68]  I. Gresser,et al.  Interferon and cell division. IX. Interferon-resistant L1210 cells: characteristics and origin. , 1974, Journal of the National Cancer Institute.

[69]  I. Gresser,et al.  Enhancement by interferon of the expression of surface antigens on murine leukemia L 1210 cells. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[70]  I. Gresser,et al.  Mechanism of the Antitumour Effect of Interferon in Mice , 1972, Nature.

[71]  K. Cantell,et al.  Quantitative studies on viral interference in suspended L cells. III. Effect of interfering viruses and interferon on the growth rate of cells. , 1962, Virology.