HOXA GENE EXPRESSION IMPLICATED IN TREATMENT RESISTANCE AND POOR PROGNOSIS IN GLIOBLASTOMA

Naomi Seidu, Edward Poluyi, Chibuikem Ikwuegbuenyi, Eghosa Morgan
  MNJ, pp. 105-110  

Abstract


This review brings into view the prognosis attributable to glioblastoma (GBM) and resistance to treatment, surgical interventions and chemotherapy seem ineffective at procuring a better prognosis for patients with the disease. Albeit there exist varying interventions for GBM, the median survival still comes to 12 to 15 months for afflicted patients, this has aroused the need for improvement in treatment success The principal goal is to create a better prognosis and have a decline in treatment resistance invariably leading to better survival rates via adequate treatment for GBM. A relationship exists between HOX genes (homeobox genes) and glioblastoma as is evident from literature. Treatment resistance has been observed in overexpression of HOX genes, the effectiveness of treatment could result from silencing these genes A series of studies have highlighted the role that HOX genes play in glioblastoma prognosis. Promotion of human glioblastoma initiation, aggressiveness, and resistance to Temozolomide has been associated with HOXA9 as shown by Pojo et al. The role of HOX gene expression in cancer stem cells should be studied as it could provide a means of designing CSC-targeted therapies, as CSCs play a part in initiation and progression of solid tumors.


Keywords


HOXA Gene- Homoebox genes Cluster A; GBM- Glioblastoma; Temozolomide; signalling pathways; RNA; Wnt.

Full Text:

PDF

References


Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma Multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev APJCP; 2017. Jan;18(1):3–9.

DOI: 10.22034/APJCP.2017.18.1.3

Agnihotri S, Burrell KE, Wolf A, Jalali S, Hawkins C, Rutka JT, et al. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Arch Immunol Ther Exp (Warsz); 2013. Feb;61(1):25–41.

DOI: 10.1007/s00005-012-0203-0

Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, et al. Epidemiologic and molecular prognostic review of glioblastoma.

Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol; 2014. Oct;23(10):1985–96. DOI: 10.1158/1055-9965.EPI-14-0275

Rock K, McArdle O, Forde P, Dunne M, Fitzpatrick D, O’Neill B, et al. A clinical review of treatment outcomes in glioblastoma multiforme--the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival? Br J Radiol; 2012. Sep;85(1017):e729-733. DOI: 10.1259/bjr/83796755

Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res Off J Am Assoc Cancer Res; 2013. Feb 15;19(4):764–72.

DOI: 10.1158/1078-0432.CCR-12-3002

Iacob G, Dinca EB. Current data and strategy in glioblastoma multiforme. J Med Life; 2009. Dec;2(4):386–93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019011/

Ohgaki H. Epidemiology of brain tumors. Methods Mol Biol Clifton NJ. 2009;472:323–42.

DOI: 10.1007/978-1-60327-492-0_14

Salvati M, Frati A, Russo N, Caroli E, Polli FM, Minniti G, et al. Radiation-induced gliomas: Report of 10 cases and review of the literature. Surg Neurol. 2003; Jul;60(1):60–7; discussion 67.

DOI: 10.1016/s0090-3019(03)00137-x

Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin; 2007. Nov;25(4):867–90, vii.

DOI: 10.1016/j.ncl.2007.07.002

Adamson C, Kanu OO, Mehta AI, Di C, Lin N, Mattox AK, et al. Glioblastoma multiforme: A review of where we have been and where we are going. Expert Opin Investig Drugs [Internet]; 2009 Aug [cited 2020 May 14];18(8):1061–83. Available from: https://www.tandfonline.com/doi/full/10.1517/13543780903052764

Nakada M, Kita D, Watanabe T, Hayashi Y, Teng L, Pyko IV, et al. Aberrant signaling pathways in glioma. Cancers; 2011. Aug 10;3(3):3242–78.

DOI: 10.3390/cancers3033242

Nelson SJ, Cha S. Imaging glioblastoma multiforme. Cancer J Sudbury Mass; 2003. Apr;9(2):134–45.

DOI: 10.1097/00130404-200303000-00009

Neurologic Manifestations of Glioblastoma Multiforme Clinical Presentation: History, Physical, Causes [Internet]. [cited 2020 May 15].

Available from:

https://emedicine.medscape.com/article/1156220-clinical

Kesari S. Understanding glioblastoma tumor biology: the potential to improve current diagnosis and treatments. Semin Oncol; 2011. Dec;38 Suppl 4:S2-10. DOI: 10.1053/j.seminoncol.2011.09.005

MP C, B E, HR S, H S, J F, M H, et al. Cancer Incidence in Five Continents Volume IX [Internet]. [cited 2020 May 14]. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Scientific-Publications/Cancer-Incidence-In-Five-Continents-Volume-IX-2007

Friedman HS, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma. Clin Cancer Res Off J Am Assoc Cancer Res; 2000. Jul;6(7):2585–97. Available from: https://pubmed.ncbi.nlm.nih.gov/10914698/

Scott J, Tsai Y-Y, Chinnaiyan P, Yu H-HM. Effectiveness of radiotherapy for elderly patients with glioblastoma. Int J Radiat Oncol Biol Phys. 2011 Sep 1;81(1):206–10. DOI: 10.1016/j.ijrobp.2010.04.033

Chang JE, Khuntia D, Robins HI, Mehta MP. Radiotherapy and radiosensitizers in the treatment of glioblastoma multiforme. Clin Adv Hematol Oncol HO; 2007. Nov;5(11):894–902, 907–15. Available from: https://pubmed.ncbi.nlm.nih.gov/18185489/

Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: A randomized clinical trial. JAMA; 2015. Dec 15;314(23):2535–43.

DOI: 10.1001/jama.2015.16669

Seymour T, Nowak A, Kakulas F. Targeting aggressive cancer stem cells in glioblastoma. Front Oncol; 2015;5:159. DOI: 10.3389/fonc.2015.00159

Shah N, Sukumar S. The Hox genes and their roles in oncogenesis. Nat Rev Cancer; 2010. May;10(5):361–71. DOI: 10.1038/nrc2826

Bhatlekar S, Fields JZ, Boman BM. HOX genes and their role in the development of human cancers. J Mol Med Berl Ger; 2014. Aug;92(8):811–23.

DOI: 10.1007/s00109-014-1181-y

Costa BM, Smith JS, Chen Y, Chen J, Phillips HS, Aldape KD, et al. Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma. Cancer Res [Internet]; 2010. Jan 15 [cited 2020 May 14];70(2):453–62. Available from:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849935/

Gaspar N, Marshall L, Perryman L, Bax DA, Little SE, Viana-Pereira M, et al. MGMT-independent temozolomide resistance in pediatric glioblastoma cells associated with a PI3-kinase-mediated HOX/stem cell gene signature. Cancer Res; 2010. Nov 15;70(22):9243–52. DOI: 10.1158/0008-5472.CAN-10-1250

Pojo M, Gonçalves CS, Xavier-Magalhães A, Oliveira AI, Gonçalves T, Correia S, et al. A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initiation, aggressiveness and resistance to temozolomide. Oncotarget [Internet]; 2015 Feb 20 [cited 2020 May 15];6(10):7657–74. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480707/

Neville SE, Baigent SM, Bicknell AB, Lowry PJ, Gladwell RT. Hox gene expression in adult tissues with particular reference to the adrenal gland. Endocr Res; 2002. Nov;28(4):669–73. DOI: 10.1081/erc-120016984

Gonçalves CS, Xavier-Magalhães A, Pojo M, Oliveira AI, Correia S, Reis RM, et al. Transcriptional profiling of HOXA9-regulated genes in human glioblastoma cell models. Genomics Data [Internet]. 2015 May 19 [cited 2020 May 14];5:54–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583997/

Quagliata L, Matter MS, Piscuoglio S, Arabi L, Ruiz C, Procino A, et al. Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatol Baltim Md; 2014. Mar;59(3):911–23. DOI: 10.1002/hep.26740

Duan R, Han L, Wang Q, Wei J, Chen L, Zhang J, et al. HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways. Oncotarget [Internet]; 2015. Jul 31 [cited 2020 May 14];6(29):27778–93. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695025/

Li Q, Dong C, Cui J, Wang Y, Hong X. Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme. J Exp Clin Cancer Res CR; 2018. Oct 30;37(1):265.

DOI: 10.1186/s13046-018-0941-x.

Se Y-B, Kim SH, Kim JY, Kim JE, Dho Y-S, Kim JW, et al. Underexpression of HOXA11 is associated with treatment resistance and poor prognosis in glioblastoma. Cancer Res Treat Off J Korean Cancer Assoc; 2017. Apr;49(2):387–98.

DOI: 10.4143/crt.2016.106


Refbacks

  • There are currently no refbacks.