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Simões BM, Santiago-Gómez A, Chiodo C, Moreira T, Conole D, Lovell S, Alferez D, Eyre R, Spence K, Sarmiento-Castro A, Kohler B, Morisset L, Lanzino M, Andò S, Marangoni E, Sims AH, Tate E, Howell SJ and Clarke RB.
Targeting STAT3 signalling using stabilised sulforaphane (SFX-01) inhibits endocrine resistant stem-like cells in ER-positive breast cancer. Oncogene. 2020 May 30.
https://doi.org/10.1038/s41388-020-1335-z.
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Dr Howell and Prof Clarke are both on Evgen's Scientific Advisory Board.
In addition, Dr Howell also works closely with the Breast Biology Group of Professor Rob Clarke and has translated the findings of the group into successful treatment trials, with publications expected in 2021
http://www.breastcentre.manchester.ac.uk/Portals/12/Documents/Manchester_Breast_Centre_Report_2019-2020.pdf
News/UPdate on SFX-01's Breast Cancer programme at anytime. Gla ;-)
Rob Clarke
@RobClarkeLab
·
3h
Check out our @MCRBreastCentre report for 2019-2020 to find out how we’re translating basic and clinical breast research into patient benefit. Mancunian research academics doing #teamscience = better research
· May 7
We are thrilled to present the latest MBC Report for 2019-2020 which highlights our recent breast research and publications.
hTtps://bit.ly/3haQQQr
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The major research interests of the group are breast development, where we focus on hormonal regulation of luminal progenitors and cancer where bone metastasis and endocrine resistance are major interests.
Recently, we established a role for the human bone microenvironment in promoting colonisation of breast cancer cells through secretion of interleukin 1 beta (IL1ß). We showed that IL1ß induces Wnt signalling in the cancer cells and that drives colony-forming activity using novel models of patient-derived bone marrow and breast cancer cells (Refs 1 & 2).
Our research on estrogen receptor-positive (ER+) breast cancer aims to identify drivers of resistance to current standard of care treatments including endocrine and CDK4/6 inhibitor therapies.
We previously established that ALDH+ cancer stem cells (CSCs) were responsible for anti-estrogen resistance driven by Notch4 receptor signalling (Simoes et al., Cell Reports, 2015), and more recently have shown that this is inhibited by peptides derived from FKBPL protein (3).
We also exploited patient-derived samples from endocrine resistant patients to demonstrate a role for PAK4 kinase in resistance and validated the efficacy of a potent kinase inhibitor currently licenced by Cancer Research UK Commercial Partnerships (4). In exciting work published in Oncogene (5), we showed that endocrine resistant ALDH+ CSCs from patients could be inhibited by a stabilised formulation of sulforaphane (SFX-01).
This research led from ‘bench to bedside’ providing the basis for the clinical trial (STEM01) in metastatic breast cancer led by MBC Medical Oncologist Sacha Howell. Finally, we used single cell gene expression analysis of endocrine resistant CSCs to establish that there is a dormant population of cells remaining after treatment that are dependent on the IL1ß signalling pathway (6).
This links to our work in bone metastasis outlined above which indicates that endocrine resistant CSCs will respond to the bone microenvironment and may be sensitive to IL1ß inhibitors such as Anakinra and Canakinumab. We hope our MBC clinical colleagues will test this in future clinical trials.