Professor Kefah Mokbel
Honorary Professor
- Biosciences
Research area(s)
Translational breast cancer research.
Clinical aspects of breast cancer research including early detection, risk-adapted treatment optimisation, and reconstructive breast surgery.
Research Interests
The molecular biology research has been focussed on the following key areas: ●The expression and regulation of telomerase and hTERT (the catalytic subunit of telomerase) in breast cancer:[In collaboration with The Brunel Institute of Cancer Genetics & Pharmacogenomics]We have demonstrated that telomerase is reactivated in most human breast cancers and its expression correlates with tumour stage and proliferation markers such as Ki- 67. The relationship between telomerase, bcl-2, P53, c-Myc and TGF-b expressions was also investigated. We showed that hTERT expression was up-regulated in human breast cancer and correlated with telomerase activity and clinical outcome. This research has led to numerous original publications in prestigious peer-reviewed journals such as: Am J Surg, Breast Cancer Research and Treatment Journal, Eur J Surg Oncol, J Natl Cancer Inst, Anti-cancer Res....We are the first group to recently investigate the role of telomere-related proteins (Pot1, Tank1, Tank2, Tin2, TRF1, TRF2, hTR, Est1, and Pinx1) in mammary carcinogenesis. This original research has been recently published in Breast Cancer Research and Treatment Journal (impact factor = 5.4).We have hypothesised and demonstrated for the first time, in the scientific literature, that APRG-1, DLEC1 and SETD2 genes behave as tumour suppressors in breast cancer. We also made a major breakthrough in identifying SETD2 asthe telomerase suppressor gene.Cyclo-oxygenase 2 (Cox-2) in human breast cancer and its relation to carcinogenesis, angiogenesis and biological behaviour.We have demonstrated that cox-2 mRNA is up-regulated in breast cancer and that its expression correlates with the hormone receptor status and angiogenesis markers. We detected over-expression in the early stages of carcinogenesis and reported a correlation between cox-2 and clinical outcome. This work has been the subject of an MS thesis expected to be submitted at the end of 2004. Our experimental data led to several original publications in prestigious peer-reviewed journals.● Chromosome 3P21 [In collaboration with The Brunel Institute of Cancer Genetics & Pharmacogenomics]
We have hypothesised and demonstrated for the first time in the scientific literature that the APRG-1, DLEC1 and SETD2 genes behave as tumour suppressors in breast cancer. We have recently made a major breakthrough in identifying SETD2 as the telomerase suppressor gene.
● IGF-1 AxisWe have shown the relative importance of the paracrine/endocrine role of IGF-1 in mammary carcinogenesis and that IGF-1mRNA expression correlates with nodal status: the best single predictor of disease behaviour in established breast cancer. We have also shown that IGF-1 up-regulates oestrogen synthesising enzymes in human breast cancer.This work has been presented internationally and has been published in peer- reviewed Journals.We investigated the role of IGF-binding proteins (1,2,3 and 7) in mammary carcinogenesis.● Oestrogen-producing enzymesWe have demonstrated that high mRNA expression of these enzymes is associated with a poor clinical outcome in human breast cancer. We have also shown that IGF-1 up-regulates these enzymes.● Osteopontins A, B and C in human breast cancerWe are currently investigating the role of osteopontins in mammary carcinogenesis● Suppressor of Cytokine Signalling (SOCS) Proteins: 1-7 in human breast cancer.● RACK1, Twist, CD44, SATB1, DELC1● PD-1 & PD-l1● Breast cancer stem cells● Autophagy pathway in breast cancer● Lamin A and B in human breast cancer [In collaboration with The Brunel Institute ofCancer Genetics & Pharmacogenomics]
We are currently investigating the role of GD2 as a potential biomarker of mammary cancer stem cells
The clinical research programme focussed on de-escalation of breast cancer surgery, wire-free localisation of non-palpable breast cancer, targeted axillary dissection,mammographic density, mammary ductoscopy, sentinel lymph node biopsy, skin- sparing mastectomy and immediate reconstruction including prepectoral ADM-assisted, breast lipofilling, genomic profiling, DCIS and risk-reducing strategies.