01 Jul 2026

Dr Bruno Simões - Winner of the BACR AstraZeneca Frank Rose Award

I have always been motivated by the idea that understanding how cancer begins and develops at the cellular level can ultimately change how we prevent and treat disease. As a breast cancer cell biologist, my research focuses on understanding how normal breast stem and progenitor cells are regulated, how these processes become altered during cancer development, and how this knowledge can be translated into new strategies to prevent breast cancer and improve patient outcomes.
I studied Microbial Biology and Genetics at the University of Lisbon, including a research training year at the Institute of Molecular Genetics in Pavia, Italy, which led me to pursue a career in research. I then completed my PhD at CICbioGUNE in Bilbao under the supervision of Dr Maria Vivanco, investigating human breast stem cell biology. During this time, I identified key embryonic regulators as markers of breast stem cells and showed that tamoxifen does not target breast cancer stem cells in estrogen receptor-positive cancers, providing a mechanistic explanation for endocrine therapy failure (Simões et al., Breast Cancer Research and Treatment, 2011). This work subsequently contributed to identifying SOX2 and SOX9 as regulators of endocrine resistance through activation of Wnt signalling in cancer stem cells.
Following my PhD and a brief postdoctoral period, I joined Professor Robert Clarke's group at the University of Manchester in 2011 to investigate how breast cancer stem cells survive endocrine therapy and drive relapse. Curiously, the name Manchester derives from the Roman “Mamucium”, meaning "breast-shaped hill". Beyond this coincidence, Manchester has a long and influential history in breast cancer research, making it an ideal place to continue my work. It was here, at The Christie Hospital, that tamoxifen was first used clinically in 1969, a drug originally synthesised by Imperial Chemical Industries (now AstraZeneca), where Frank Rose played an important role in encouraging the company's commitment to cancer research.
Through a series of studies, I identified key signalling pathways that sustain the endocrine therapy-resistant cancer stem cells. I showed that NOTCH4 inhibition suppresses their activity (Simões et al, Cell Reports, 2015), and that targeting STAT3 with SFX-01 eliminates resistant cells, providing preclinical rationale for the STEM phase II clinical trial in advanced ER-positive breast cancer (Simões et al, Oncogene, 2020). I also identified IL1R1 signalling as another vulnerability and demonstrated that it can be targeted using the clinically approved drug anakinra (Sarmiento-Castro et al, Stem Cell Reports, 2020). Together, these studies established a framework for translating mechanistic insight into therapeutic strategies that could improve outcomes for patients with resistant disease.
While my earlier work focused on therapy resistance, my more recent research has shifted toward understanding how breast cancer risk arises and whether it can be intercepted before disease develops. Erasmus’ 16th-century idea that “prevention is better than cure” has become a guiding principle in my work, which focuses on identifying and targeting the earliest events that shape cancer risk. This direction culminated in my recent publication, working with Professor Sacha Howell and Professor Robert Clarke, where we demonstrated that pharmacological antagonism of the progesterone receptor reduces mammographic density, a well-established risk factor for breast cancer, alongside suppression of luminal progenitor cell activity (Simões et al, Nature, 2025). By integrating clinical samples with single-cell and molecular analyses, this work shows how progesterone signalling shapes the normal breast microenvironment and highlights it as a target for breast cancer prevention in premenopausal women at increased risk, where preventive options remain limited.
Throughout my career, I have combined mechanistic studies with human tissue and clinically relevant models to ensure that my research remains closely linked to patient disease. This has only been possible through close collaboration with clinicians, colleagues, students and international partners, helping translate fundamental biological discoveries into clinical studies and new opportunities for improving breast cancer prevention and treatment. 
I am currently a Principal Investigator at the Manchester Breast Centre and at the recently launched Prevent Breast Cancer Research Unit, funded by the Prevent Breast Cancer charity, where I lead research aimed at understanding the biology underlying breast cancer risk factors, including hormonal exposure and mammographic density. By analysing tissue from prevention trials and women at increased risk, my aim is to identify the earliest molecular and cellular changes in the normal breast that determine cancer risk and translate these findings into rational chemoprevention strategies.
I am grateful to BACR and AstraZeneca for this recognition and to all colleagues and students who have contributed to this work. For me, the BACR/AstraZeneca Young Scientist Frank Rose Award represents not only an acknowledgement of past scientific achievements, but also an encouragement to continue advancing our understanding of breast cancer risk biology, with the ultimate goal of preventing cancer before it begins.
 

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