Since being appointed as a lecturer and consequently senior lecturer and professor in Molecular Oncology and then as an anniversary chair professor in Molecular Pathology and Cancer Therapeutics in University of Bradford, Prof El-Tanani has made seminal contributions to the understanding of cancer metastasis - the spread of cancer from the primary tumour to distant organs and sites. Prof El-Tanani work, primarily focuses on tumour progression and metastasis, has changed many research paradigms in the field, as this complex process is responsible for the majority of cancer deaths. Once cancer has spread, current treatments ultimately fail for most patients. Furthermore, metastasis can be particularly insidious as it may develop after variable and unpredictable periods of tumour dormancy. Prof El-Tanani research program strives for a better understanding of metastasis and thus has the potential to improve cancer patient survival and quality of life. Prof El-Tanani work concentrates on two broad areas of cancer progression and metastasis. First, he has a major program aimed at understanding the biology of the cancer progression and metastatic process. This program uses animal models, novel-imaging approaches to “watch” the process, and molecular approaches to better understand how the process is regulated. Second, he has a major program focused on the secreted, integrin-binding protein osteopontin (OPN) and its target gene Ran GTPase (Ran). This program has complementary experimental and clinical arms, focused on learning how OPN, Ran and their target genes increase the metastatic potential of cancer cells, and on the development and uses of assays to measure OPN, Ran and their targets levels in tumours, which in turn could represent a valuable new predictive biomarker. Prof El-Tanani has shown that OPN and Ran contribute functionally to the malignant behaviour of cancer cells, and that measuring OPN and Ran levels in patients may provide clinically useful information.
- El-Tanani, M.K., et al., Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression. Oncogene, 2010. 29(5): p. 752-62.
- El-Tanani, M.K., et al., Osteopontin can act as an effector for a germline mutation of BRCA1 in malignant transformation of breast cancer-related cells. Cancer Sci, 2010. 101(6): p. 1354-60.3.
- Kurisetty, V.V., et al., RAN GTPase is an effector of the invasive/metastatic phenotype induced by osteopontin. Oncogene, 2008. 27(57): p. 7139-49.
- Kurisetty, V.V., et al., Identification of genes differentially expressed between benign and osteopontin transformed rat mammary epithelial cells. BMC Res Notes, 2009. 2: p. 15.
- Yuen, H.F., et al., Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling. Oncotarget, 2016. 7(46): p. 75854-75864.
- Yuen, H.F., et al., RanGTPase: a candidate for Myc-mediated cancer progression. J Natl Cancer Inst, 2013. 105(7): p. 475-88.
The scientific understanding of the role of Ran protein as an important therapeutic target and biomarker in cancer has been developed by himself and his team to the level of a platform capability. Ran protein is expressed in tumours which have high drug resistance and metastatic potential, so it is an excellent biomarker for prediction of patient drug response, early predict if the patient will develop metastasis and on patient survival. This is most relevant in the case of triple negative breast cancer, where conventional therapies or prognostic/predictive biomarkers are not available. Moreover, in non-small cell lung cancer, Ran expression can indicate the emergence of drug resistance. Ran itself is a therapeutic target for treatment of cancers with drug resistant or high metastatic potential. Thus, the Ran platform encompasses both biomarker technology for use in predictive/ companion diagnostics and targeted therapeutics. Prof El-Tanani has a growing portfolio of IP in this area and the various arms of the Ran platform are the subject of several grant applications including MRC, Breast Cancer Now and Wellcome Trust and others.
7.Doherty, K.J., et al., RAN GTPase as a Target for Cancer Therapy: Ran Binding Proteins. Curr Mol Med, 2011.
8. Haggag, Y.A., et al., Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells. Int J Pharm, 2017. 521(1-2): p. 40-53.
9. Yuen, H.F., et al., Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. Clin Cancer Res, 2012. 18(2): p. 380-91
It is also apparent that the pharmaceutical industry will benefit from an improved understanding of the mechanisms underlying Ran targets, as this could help improve the design of new drugs and identify new applications for existing agents. Therefore, disseminating results to a wide range of researchers and clinical staff is key to achieving maximum economic and societal benefit from my program. Prof El-Tanani has published more than 80 peer-reviewed papers, an average of 6 per year in high impact factor journals in recent years. Bibliometric analysis reveals that the research work carried out in his laboratory has high scientific impact and is frequently cited by many other researchers. Prof El-Tanani has been invited to present at numerous international, national, and local conferences.