HXR9

Potential targets for novel therapies include proteins involved in cell growth and signalling within the cell. These include proteins, so called transcription factors, that have previously been identified as being switched on in cancer and therefore lead to unchecked growth of cells. Of particular note are the HOX genes, a family of proteins normally involved in development of the nervous system in the embryo. We have designed a small protein, HXR9, which is able to pass into the cell and disrupt the interaction between HOX and a second protein, PBX. This protein is able to cause cell death when added to cancer cells in culture and also can also reduce or prevent the growth of melanoma, breast, lung, ovarian and prostate tumours.

The potential of HXR9 has now been realised and a start-up company, HOX Therapeutics, has been established in order to develop this novel therapy further and carry out clinical trials in man.  A huge amount of work has been carried out by our group to study HOX genes in cancer cells and also assess HXR9 in a range of cancers. This is reflected in the publication of many papers in peer reviewed journals:

  1. Morgan R, El-Tanani M, Hunter KD, Harrington KJ, Pandha HS. Targeting HOX/PBX dimers in cancer. Oncotarget. 2017 Mar 7.
  2. Kelly Z, Moller-Levet C, McGrath S, Butler-Manuel S, Kavitha Madhuri T, Kierzek AM, Pandha H, Morgan R, Michael A. The prognostic significance of specific HOX gene expression patterns in ovarian cancer. Int J Cancer. 2016 Oct 1;139(7):1608-17
  3. Morgan R, Simpson G, Gray S, Gillett C, Tabi Z, Spicer J, Harrington KJ, Pandha HS. HOX transcription factors are potential targets and markers in malignant mesothelioma. BMC Cancer. 2016 Feb 11;16:85
  4. Morgan R, Simpson G, Gray S, Gillett C, Tabi Z, Spicer J, Harrington KJ, Pandha HS. HOX transcription factors are potential targets and markers in malignant mesothelioma. BMC Cancer. 2016 Feb 11;16:85
  5. Morgan R, Boxall A, Harrington KJ, Simpson GR, Michael A, Pandha HS. Targeting HOX transcription factors in prostate cancer. BMC Urol. 2014 Feb 5;14(1):17
  6. Li Z, Zhang Z, Li Y, Arnovitz S, Chen P, Huang H, Jiang X, Hong GM, Kunjamma RB, Ren H, He C, Wang CZ, Elkahloun AG, Valk PJ, Döhner K, Neilly MB, Bullinger L, Delwel R, Löwenberg B, Liu PP, Morgan R, Rowley JD, Yuan CS, Chen J. PBX3 is an important cofactor of HOXA9 in leukemogenesis. Blood. Blood. 2013 Feb 21;121(8):1422-31.
  7. Morgan R, Boxall A, Harrington KJ, Simpson GR, Gillett C, Michael A, Pandha HS Targeting the HOX/PBX dimer in breast cancer. Breast Cancer Res Treat. 2012 Sep 30
  8. Alharbi RA, Pettengell R, Pandha HS, Morgan R. The role of HOX genes in normal hematopoiesis and acute leukemia. Leukemia. 2012 Dec 5
  9. Kelly ZL, Michael A, Butler-Manuel S, Pandha HS, Morgan RG. HOX genes in ovarian cancer. J Ovarian Res. 2011 Sep 9;4:16.
  10. Gray S, Pandha HS, Michael A, Middleton G, Morgan R. HOX Genes in Pancreatic Development and Cancer. Journal of the pancreas. 2011 May 6;12(3):216-9
  11. Daniels TR, Neacato, II, Rodriguez JA, Pandha HS, Morgan R, Penichet ML. Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells. Leukemia. 2010 Sep;24(9):1555-65.
  12. Morgan R, Plowright L, Harrington KJ, Michael A, Pandha HS. Targeting HOX and PBX transcription factors in ovarian cancer. BMC Cancer. 2010;10:89.
  13. Plowright L, Harrington KJ, Pandha HS, Morgan R. HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer). Br J Cancer. 2009 Feb 10;100(3):470-5.
  14. Morgan R and Whiting K. Differential expression of HOX genes upon activation of leukocytre sub-populations. Int J Haematol. 2008;87(256-249).
  15. Shears L, Plowright L, Harrington K, Pandha HS, Morgan R. Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell death in the renal cancer lines CaKi-2 and 769-P. J Urol. 2008 Nov;180(5):2196-201
  16. Morgan R, Pirard PM, Shears L, Sohal J, Pettengell R, Pandha HS. Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Res. 2007 Jun 15;67(12):5806-13. 7.543