The following is an abstract of a review of the HOX genes’ role in cancer, published in Oncotarget in March 2017.
Targeting HOX/PBX dimers in cancer
Richard Morgan1, Mohamed El-Tanani1, Keith D. Hunter2, Kevin J. Harrington3 and Hardev S. Pandha4
1 Institute of Cancer Therapeutics, Faculty of Life Sciences, University of Bradford, UK
2 Unit of Oral and Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Sheffield, UK
3 Targeted Therapy Team, Chester Beatty Laboratories, The Institute of Cancer Research, London, UK
4 Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
Correspondence to: Richard Morgan, email: firstname.lastname@example.org
Keywords: HOX, PBX, HXR9, targeted therapy, biomarker
Received: December 08, 2016 Accepted: February 23, 2017 Published: March 07, 2017
The HOX and PBX gene families encode transcription factors that have key roles in establishing the identity of cells and tissues in early development. Over the last 20 years it has become apparent that they are also dysregulated in a wide range of solid and haematological malignancies and have a predominantly pro-oncogenic function. A key mode of transcriptional regulation by HOX and PBX proteins is through their interaction as a heterodimer or larger complex that enhances their binding affinity and specificity for DNA, and there is growing evidence that this interaction is a potential therapeutic target in malignancies that include prostate, breast, renal, ovarian and lung cancer, melanoma, myeloma, and acute myeloid leukaemia. This review summarises the roles of HOX and PBX genes in cancer and assesses the therapeutic potential of HOX/PBX dimer inhibition, including the availability of biomarkers for its application in precision medicine.
List of publications below
McGrath SE, Annels N, Madhuri TK, Tailor A, Butler-Manuel SA, Morgan R, Pandha H, Michael A. Engrailed-2 (EN2) - a novel biomarker in epithelial ovarian cancer.BMC Cancer. 2018 Oct 3;18(1):943. doi: 10.1186/s12885-018-4816-5. PubMed PMID:30285763.
Platais C, Radhakrishnan R, Ebensberger SN, Morgan R, Lambert DW, Hunter K. Targeting HOX-PBX interactions causes death in oral potentially malignant and squamous carcinoma cells but not normal oral keratinocytes. BMC Cancer 2018;18:723
Morgan R, Pandha H. HOX transcription factors and the prostate tumor microenvironment. J Cancer Metastasis Treat 2017;3:278-87. | doi:10.20517/2394-4722.2017.31
Kelly Z, Morgan R, Pandha H, Michael A. The prognostic significance of HOX genes in ovarian cancer. Int J Cancer. 2016;139(7):1608-17. doi:10.1002/ijc.30204
Alharbi RA, Pandha HS, Simpson GR, Pettengell R, Poterlowicz K, Thompson A, Harrington K, El-Tanani M, Morgan R. Inhibition of HOX/PBX dimer formation leads to necroptosis in acute myeloid leukemia cells. Oncotarget 2017; 8:89566-89579 https://doi.org/10.18632/oncotarget.20023
Morgan R, El-Tanani M. HOX genes as potential markers of circulating tumor cells. Current Molecular Medicine 2016 16(4) :322-327 PubMed PMID: 26980702.
Morgan R, Harrington K, Simpson GR, Gillett C, Tabi Z, Spicer J, Michael A, Pandha HS. HOX transcription factors are potential therapeutic targets in malignant mesothelioma. BMC Cancer 2016;16:85
Platais C, Hakami F, Darda L, Lambert DW, Morgan R, Hunter KD. The role of HOX genes in head and neck squamous cell carcinoma. J Oral Pathol Med. 2015 Dec 14.doi: 10.1111/jop.12388. Review. PubMed PMID: 26661059.
Darda L, Hakami F, Morgan R, Murdoch C, Lambert DW, Hunter KD. The role of HOXB9 and miR-196a in Head and Neck Squamous Cell Carcinoma. PLoS One. 2015 10(4):e0122285. doi: 10.1371/journal.pone.0122285.
Morgan R, Boxall A, Harrington K, Waters V, Simpson G, Michael A, Pandha HS. Targeting HOX transcription factors in prostate cancer. BMC Urol. 2014 Feb 5;14(1):17 doi: 10.1186/1471-2490-14-17.
Ando H, Natsume A, Senga T, Watanabe R, Ito I, Ohno M, Iwami K, Ohka F, Motomura K, Saito K, Morgan R, Wakabayashi T. Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma. Cancer Chemother Pharmacol. 2014 Jan;73(1):53-60. doi: 10.1007/s00280-013-2316-5.
Errico MC, Felicetti F, Bottero L, Mattia G, Boe A, Felli N, Petrini M, Bellenghi M, Pandha HS, Calvaruso M, Tripodo C, Colombo MP, Morgan R, Carè A. The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway. Int J Cancer. 2013 Aug 15;133(4):879-92. doi: 10.1002/ijc.28097. Epub 2013 Mar 13.
Li Z, Zhang Z, Li Y, Chen P, Arnovitz S, Huang A, Jiang X, He C, Dohner K, Neilly MB, Wang C-Z, Bullinger L, Valk PJM, Delwel R, Lowenberg R, Morgan R, Yuan C, Rowley JD, Chen J. The HOXA/PBX3 axis is a prognostic biomarker and druggable target in cytogenetically abnormal acute myeloid leukaemia. Blood 2013 Feb 21;121(8):1422-31. doi: 10.1182/blood-2012-07-442004. Epub 2012 Dec 20.
Morgan R, Boxall A, Harrington K, Simpson GR, Michael A, Pandha HS. Targeting the HOX / PBX dimer in breast cancer. Breast Cancer Research and Treatment 2012, 136: 389-398. DOI: 10.1007/s10549-012-2259-2
Alharbi R, Pettengell R, Pandha HS, Morgan R. The role of HOX genes in normal hematopoiesis and acute leukemia. Leukemia 2013; 27:1000-8. doi: 10.1038/leu.2012.356.
Morgan R. HOX transcription factors as biomarkers in cancer. European Pharmaceutical Review. 2011 Oct; 5(16): 17-20
Kelly ZL, Michael A, Butler-Manuel S, Pandha HS, Morgan R. HOX genes in Ovarian Cancer. J Ovarian Res. 2011 Sep 9;4(1):16.
Gray S, Pandha HS, Michael A, Middleton G, Morgan R. HOX genes in pancreatic development and cancer. JOP. 2011 May 6;12(3):216-9.
Daniels T, Neacato I, Rodriguez J, Pandha H, Morgan R, Penichet M (2010) Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells. Leukemia 24, 1555-1565.
Morgan R, Plowright L, Harrington KJ, Michael A, Pandha HS. Targeting HOX and PBX transcription factors in ovarian cancer. BMC Cancer 2010 March 10; 89(10).
Plowright L, Harrington KJ, Pandha HS, Morgan R. (2009). HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer). Br J Cancer. 100: 470-475.
Shears L, Plowright L, Harrington K, Pandha H, Morgan R. (2008). Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell death in the renal cancer lines CaKi-2 and 769-P. J Urology 180, 2196-2201.
Morgan R, Pirard P, Shears S, Sohal S, Pettengell R and Pandha HS (2007). Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Research 67, 5806-5813.