Components of the TGF- β superfamily have been well established in their intricate and multifaceted roles in cancer progression and survival. The TGF- β s have been targeted therapeutically in an attempt to modify complex tumour networks to favour cancer cell destruction. Goals of these therapies are often to attack the “hallmarks” of cancer: characteristics acquired by cancer cells via re-wiring or manipulating existing biological pathways to their survival advantage. Of the multitude of targeted therapies currently available, viral therapies have shown much promise in their efficacy of treatment. This review highlights current viral therapies targeting members of the TGF- β superfamily, with a focus on the strengths and limitations associated with this form of targeted cancer therapy.
McEntee, M.F., Ziegler, C., Reel, D., et al. (2008) Dietary n-3 polyunsaturated fatty acids enhance hormone ablation therapy in androgen-independent prostate cancer. American Journal of Pathology, 173, 256-268. http://dx.doi.org/10.2353/ajpath.2008.070989
Chu, G.C., Dunn, N.R., Anderson, D.C., et al. (2004) Differential requirements for Smad4 in TGFB-dependent patterning of the early mouse embryo. Development, 131, 3501-3512. http://dx.doi.org/10.1242/dev.01248
Fields, S.Z., et al. (2013) Activin receptor antagonists for cancer-related anaemia and bone disease. Expert Opinion on Investigational Drugs, 22, 87-101. http://dx.doi.org/10.1517/13543784.2013.738666
Levy, L. and Hill, C.S. (2005) Smad4 dependency defines two classes of transforming growth factor B (TGF-B) target genes and distinguishes TGF-B induced epithelialmesenchymal transition from its antiproliferative and migratory responses. Molecular and Cellular Biology, 25, 8108-8125. http://dx.doi.org/10.1128/MCB.25.18.8108-8125.2005
Attisano, L. and Wrana, J.L. (2002) Signal Transduction by the TGF-B superfamily. Science, 296, 1646-1647. http://dx.doi.org/10.1126/science.1071809
Heldin, C.H., Miyazono, K. and Dijke, P.T. (1997) TGFB signalling from cell membrane to nucleus through SMAD proteins. Nature, 390, 465-471. http://dx.doi.org/10.1038/37284
Derynck, R. and Zheng, Y.E. (2003) Smad-dependent and Smad-independent pathways in TGFB family signalling. Nature, 425, 577-584. http://dx.doi.org/10.1038/nature02006
Ramel, M.C. and Hill, C.S. (2012) Spatial regulation of BMP activity. FEBS Letters, 586, 1929-1941. http://dx.doi.org/10.1016/j.febslet.2012.02.035
Mesnard, D., Guzman-Ayala, M. and Constam, D.B. (2006) Nodal specifies embryonic visceral endoderm and sustains pluripotent cells in the epiblast before overt axial patterning. Development, 133, 2497-2505.
Ogawa, K., et al. (2007) Activin-Nodal signalling is involved in propagation of mouse embryonic stem cells. Journal of Cell Science, 120, 55-65. http://dx.doi.org/10.1242/jcs.03296
Wu, Z., et al. (2008) Combinatorial signals of activin/nodal and bone morphogenic protein regulate the early lineage segregation of human embryonic stem cells. The Journal of Biological Chemistry, 283, 24991-25002. http://dx.doi.org/10.1074/jbc.M803893200
Topczewska, J.M., et al. (2006) Embryonic and tumorigenic pathways converge via nodal signalling: Role in melanoma aggressiveness. Nature Medicine, 12, 925-932. http://dx.doi.org/10.1038/nm1448
Bujis, J.T., et al. (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in Vivo. American Journal of Pathology, 171, 1047-1057. http://dx.doi.org/10.2353/ajpath.2007.070168
Kingsley, D.M. (1994) The TGF-beta superfamily: New members, new receptors, and new genetic tests of function in different organisms. Genes & Development, 8, 133-146. http://dx.doi.org/10.1101/gad.8.2.133
Massague, J. and Gomis, R.R. (2006) The logic of TGFB signalling. FEBS Letters, 12, 2811-2820. http://dx.doi.org/10.1016/j.febslet.2006.04.033
Katusno, Y., et al. (2008) Bone morphogenetic protein signalling enhances invasion and bone metastasis of breast cancer cells through Smad pathway. Oncogene, 27, 6322-6333. http://dx.doi.org/10.1038/onc.2008.232
Kang, H.Y., et al. (2001) From transforming growth factor-B signalling to androgen action: Identification of Smad3 as an androgen receptor coregulator in prostate cancer cells. PNAS, 90, 3018-3023. http://dx.doi.org/10.1073/pnas.061305498
Iyer, S., et al. (2005) Targeting TGF-B Signaling for Cancer Therapy. Cancer Biology & Therapy, 4, 261-266. http://dx.doi.org/10.4161/cbt.4.3.1566
Schlingensiepen, K.H., et al. (2004) The TGFbeta1 antisense oligonucleotide AP 11014 for treatment of nonsmall cell lung colorectal and prostate cancers: Preclinical studies. Journal of Clinical Oncology, 22, 31-32.
Seth, P., et al. (2006) Development of oncolytic adenovirus armed with a fusion of soluble transforming growth factor B receptor II and human immunoglobulin Fc for breast cancer therapy. Human Gene Therapy, 17, 1152-1160. http://dx.doi.org/10.1089/hum.2006.17.1152
Thalmann, G.N., et al. (2000) LNCaP progression model of human prostate cancer: Androgen-independence and osseous metastasis. Prostate, 44, 91-103. http://dx.doi.org/10.1002/1097-0045(20000701)44:2 3.0.CO;2-L
Lasaro, M.O. and Ertl, H.C. (2009) New insights on adenovirus as vaccine vectors. Molecular Therapy, 17, 1333-1339. http://dx.doi.org/10.1038/mt.2009.130
Khare, R., et al. (2011) Advances and future challenges in adenoviral vector pharmacology and targeting. Current Gene Therapy, 11, 241-258. http://dx.doi.org/10.2174/156652311796150363
Hu, Z., et al. (2012) Systemic delivery of oncolytic adenoviruses targeting transforming growth factor-b inhibits established bone metastasis in a prostate cancer mouse model. Human Gene Therapy, 23, 1-12. http://dx.doi.org/10.1089/hum.2012.040
Oh, S., et al. (2013) Transforming growth factor-B gene silencing using adenovirus expressing using adenovirus expressing TGF-B1 or TGF-B2 shRNA. Cancer Gene Therapy, 20, 94-100. http://dx.doi.org/10.1038/cgt.2012.90
Freytag, S.O., et al. (2003) Phase I study of replication-competent adenovirus-mediated double-suicide gene therapy in combination with conventional-dose three-dimensional conformal radiation therapy for the treatment of newly diagnosed, intermediate-to high-risk prostate cancer. Cancer Research, 63, 7497-7506.
Lubaroff, D.M., et al. (2006) Clinical protocol: Phase I study of an adenovirus/prostate-specific antigen vaccine in men with metastatic prostate cancer. Human Gene Therapy, 17, 220-229.
Shobana, R., et al. (2013) Prostate-specific antigen-retargeted recombinant newcastle disease virus for prostate cancer virotherapy. Journal of Virology, 87, 3792-3800. http://dx.doi.org/10.1038/cgt.2012.90
Sun, A., et al. (2009) Adeno-associated virus-delivered short hairpin-structured RNA for androgen receptor gene silencing induces tumour eradication of prostate cancer xenografts in nude mice: A preclinical study. Cancer Therapy, 126, 764-774.
Pan, J.G., et al. (2012) The adeno-associated virus-mediated HSV-TK/GCV suicide system: A potential strategy for the treatment of bladder carcinoma. Medical Oncology, 29, 1938-1947. http://dx.doi.org/10.1007/s12032-011-0091-x
Eertwegh, A.J.M., et al. (2012) Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: A phase 1 dose-escalation trial. Lancet Oncology, 13, 509-517. http://dx.doi.org/10.1016/S1470-2045(12)70007-4
Manno, C.S., et al. (2003) AAV-mediated factor IX gene transfer in skeletal muscle in patients with severe haemophilia B. Blood, 101, 2963-2972. http://dx.doi.org/10.1182/blood-2002-10-3296
Manno, C.S., et al. (2006) Successful transduction of liver in haemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nature Medicine, 12, 342-347. http://dx.doi.org/10.1038/nm1358