Preclinical Molecular Imaging Group

Dr Gabriela Kramer-Marek’s group uses cutting-edge biomedical imaging techniques to gain information about the way particular genes drive cancer progression.

Our group’s long-term goal is to develop specific biomarkers for detecting cancers and to evaluate these biomarkers in pre-clinical cancer models

Notwithstanding the remarkable clinical success of mAb-based treatment regimens, not all patients benefit from them. This can be attributed, at least in part, to the complexity of the tumour microenvironment and its considerable heterogeneity both in terms of the tumour and non-tumour cell components. These phenomena represent a huge challenge in identifying predictive biomarkers and stratifying patient populations for personalised therapy approaches.

Therefore, there is an urgent need to develop assays that will help in three ways:

  1. accurate patient selection
  2. understanding intrinsic resistance mechanisms or the emergence of acquired resistance following treatment initiation and
  3. choosing the most effective combination regimen in circumstances in which single-agent therapies are insufficiently effective.

Currently, the baseline expression level of antigens targeted by therapeutic mAbs can be analysed by methods such as: immunohistochemistry (IHC), flow cytometry, proteomics, or next-generation sequencing of tumour tissues acquired at diagnostic biopsy or intra-operatively. These techniques aid our understanding of how cancer cells adapt to treatment and become resistant, but such methods are inherently invasive, prone to sampling errors caused by inter- and intra-tumour heterogeneity of receptor expression within analysed biopsy specimens and do not lend themselves readily to repeated sampling.

Positron emission tomography (PET), using radiolabelled mAbs, antibody fragments or engineered protein scaffolds (immuno-PET), has the potential to acquire information non-invasively and can be highly complementary to analyses based on tissue acquisition. Accordingly, immuno-PET agents might accurately identify the presence and accessibility of the target and provide a rapid assessment of tumour response to a variety of treatments in a timely fashion (e.g. within 1-2 weeks of treatment initiation).

Furthermore, immuno-PET agents can provide information about the heterogeneity of both target expression and therapeutic response, which are increasingly recognised as key factors in treatment resistance. This especially relates to patients with advanced disease in whom target expression may vary from site to site and a biopsy of a single local or metastatic deposit may not accurately reflect the situation across the entire disease burden. Although introduction of immuno-PET into routine clinical practice may add complexity and increase costs, with appropriate use this imaging modality has the potential to identify patients likely to benefit from therapy and assess the efficacy of novel target-specific drugs.

Against this background, our research focuses on the development and characterisation of targeted-PET radiotracers, including protein-based theranostic agents that enable smart monitoring of immunotherapies and expand opportunities for personalised medicine approaches.

Early diagnosis and individualized therapy have been recognized as crucial for the improvement of cancer treatment outcome. While proper molecular characterization of individual tumour types facilitates choice of the right therapeutic strategies, early assessment of tumour response to therapy could allow the physicians to discontinue ineffective treatment and offer the patient a more promising alternative. Therefore, the role of molecular imaging in elucidating molecular pathways involved in cancer progression and the ability to select the most effective therapy based on the unique biologic characteristics of the patient and the molecular properties of a tumour are undoubtedly of paramount importance.

The mission of this group is to investigate innovative imaging probes and apply them to novel orthotopic or metastatic models that are target driven, to gain information of the way particular oncogenes drive cancer progression through signalling pathways that can be imaged in vivo and, correlate it with target level ex vivo. Such an approach enables non-invasive assessment of biochemical target levels, target modulation and provides opportunities to optimize the drug dosing for maximum therapeutic effect, which leads to the development of better strategies for the more precise delivery of medicine.

The long term goal of our research is to develop specific imaging cancer biomarkers, especially for positron emission tomography (PET) as well as optical imaging and, evaluate these biomarkers in pre-clinical cancer models. Significant efforts are directed towards validating biomarkers for early prediction of treatment response, with the focus on new targeted therapies (such as inhibition of cell signalling pathways).

Our initial portfolio of imaging agents include radiolabelled affibody molecules, TK inhibitors and, conventional tracers that monitor universal markers of tumour physiology.

We are actively supported by other groups from the Division of Radiotherapy and Imaging as well as the Division of Cancer Therapeutics. Moreover, our close association with The Royal Marsden NHS Foundation Trust enables rapid translation of our research to early clinical studies and ensures a fast transition of know-how from the research laboratory to the patient bedside.

Dr Gabriela Kramer-Marek

Group Leader:

Preclinical Molecular Imaging Gabriela Kramer-Marek

Dr Gabriela Kramer-Marek is investigating new ways of molecular imaging in order to predict an individual patient’s response to treatment. Before moving to the ICR, she developed a new approach for non-invasive assessment of HER2 expression in breast cancer.

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Researchers in this group

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Phone: 020 3437 6376

Email: [email protected]

Location: Sutton

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Phone: +44 20 3437 6785

Email: [email protected]

Location: Sutton

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Phone: 020 3437 6356

Email: [email protected]

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Phone: +44 20 3437 6857

Email: [email protected]

Location: Sutton

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Phone: 020 3437 4549

Email: [email protected]

Location: Sutton

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Dr Gabriela Kramer-Marek's group have written 63 publications

Most recent new publication 10/2024

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Recent discoveries from this group

31/01/25

Hormone replacement therapy taken at age 50 for up to 5 years only modestly increases the risk of breast cancer, even for women with a strong family history of the disease, according to a new risk model published in the British Journal of General Practice.

While it is known that hormone replacement therapy (HRT) can increase the risk of breast cancer – but that this risk is quite low for most women – there has been concern from GPs and women themselves that it might be unsafe for women with a strong family history of the disease.

Women have around a ten per cent risk of developing breast cancer by the age of 80, which can be doubled or more where there is a strong family history of breast cancer.

The model considers family history of breast cancer

Researchers at The Institute of Cancer Research, London, the University of Cambridge, and the University of Manchester, developed a risk model which integrates data about the relative risk of breast cancer associated with different types and durations of HRT, with data about age-related breast cancer risk according to the number of family members with breast cancer.

The researchers considered three family profiles:

  • Modest family history (a mother or sister with breast cancer at the age of 60)
  • Intermediate family history (a mother or sister with breast cancer at the age of 40)
  • Strong family history (both a mother and a sister with breast cancer at the age of 50)

Combined-cyclical HRT (where oestrogen is given daily and progestogen is given for 10–14 days) is most commonly prescribed at the start of menopausal symptoms.

For some, short-term HRT use increases breast cancer risk by 1.2 per cent

The modelling revealed that short-term (five years) of combined-cyclical HRT increases the absolute risk of breast cancer by age 80 by 1.2 per cent for an average woman in the population, and by 2.8 per cent for a woman with a strong breast cancer family history:

  • For the average woman in the population not taking HRT, the risk of developing breast cancer by age 80 is estimated to be 9.8 per cent. With five years of HRT between the ages of 50–55, this increases to 11 per cent.
  • For the exemplar woman with strong family history, not taking HRT, the risk of developing breast cancer by age 80 is estimated to be 19.6 per cent. With five years of combined-cyclical HRT, this increases to 22.4 per cent.

Taking HRT for longer increases the risk of breast cancer

The risk of breast cancer is known to increase more dramatically if HRT is taken for longer or at an older age. The model indicates that 10 years of HRT at age 50-60 increases the risk of developing breast cancer by an estimated 2.6 per cent for the average woman in the population, and 5.6 per cent for the exemplar woman with strong family history of breast cancer.

The increased risk of dying from breast cancer due to five years of hormone replacement therapy is relatively low:

  • For the average woman in the population, this risk increases from an estimated 1.7 per cent to 1.8 per cent.
  • For the exemplar woman with strong family history of breast cancer, this risk increases from an estimated 3.2 per cent to 3.5 per cent.

This means that for 343 women with an equivalently strong family history, approximately 11 would die from breast cancer diagnosed aged 50–80 if none were taking HRT. If all these women took five years of combined-cyclical HRT at age 50, approximately one additional woman of the 343 would die from breast cancer. 

The researchers also examined the risk of taking oestrogen-only HRT and found that the risk is more modest than for combined cyclical HRT, while the risk is slightly greater for continuous progestogen HRT.

The risk model will help women to decide whether to use HRT

The modelling is intended to aid shared decision-making between women and their GPs. Some women may want to avoid any further increase in risk of breast cancer, if they know themselves to already be at a higher risk due to their family history of disease. For other women for whom the symptoms of menopause are debilitating, this relatively modest increase in their individual risk of developing and dying of breast cancer after a short use of HRT may be acceptable.

‘The risk of dying from breast cancer remains low’

Professor Clare Turnbull, Professor of Translational Cancer Genetics at The Institute of Cancer Research, London, and Consultant in Clinical Cancer Genetics at The Royal Marsden NHS Foundation Trust, said:

“We know some women are concerned about taking hormone replacement therapies due to the increased risk of breast cancer. Our modelling may provide reassurance that taking these treatments only increases that risk quite modestly, even for those women already with an increased risk of breast cancer due a family history of disease. The risk of dying from breast cancer remains low, and our modelling shows only a quite modest added risk from taking hormone replacement therapies. 

“What is key is that women and their doctors have the data with which to make informed decisions around the risks and benefits of taking HRT to treat menopausal symptoms. It’s also important to remember that the risk of developing breast cancer is influenced by many other factors, some of which are modifiable.”

Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:

“This modelling provides an insight into the influence that hormone replacement therapy can have in increasing the risk of developing breast cancer. It’s important to have the evidence to help women make a more informed decision about their use of hormone replacement therapy. I hope to see future epidemiological studies assess this impact in people, as we know that the risk of developing any type of cancer is complex and determined by a number of factors working together.”