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

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Location: Sutton

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Phone: +44 20 3437 6785

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Location: Sutton

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Phone: 020 3437 6356

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Phone: +44 20 3437 6857

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Location: Sutton

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Phone: 020 3437 4549

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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

19/02/25

Offering genetic testing to patients with the blood cancer myeloma would help doctors spot those with the most aggressive forms of the disease so that their cancer can be targeted more effectively, say scientists.

With effective treatment, more than half of myeloma patients will survive their disease for five years or more. However, between 20-25 per cent have specific genetic changes in their cancer cells that make the disease more aggressive and harder to treat. High-risk patients typically see their disease come back much earlier after diagnosis, unless given tailored treatment.

Defining ‘double hit’ myeloma

Now, new research led by The Institute of Cancer Research, London, and The University of Leeds has shown that patients who carry two or more genetic abnormalities – known as ‘double hit’ myeloma – are at more than twice the risk of their disease progressing early and almost three times more likely to die earlier with current standard treatment, compared to patients with a standard form of the illness.

The findings, published in the Journal of Clinical Oncology, have highlighted the high level of unmet need in this group of patients, and led to calls for better access to early genetic testing and personalised treatments.

Myeloma is a blood cancer which starts in the plasma cells and each year approximately 5,900 people are diagnosed in the UK, according to blood cancer charity Myeloma UK.

Standard treatments include targeted drugs, chemotherapy and stem cell transplants.

There are typically around five or six key genetic changes, known as High-Risk Cytogenetic Abnormalities (HRCAs) that are used to classify myeloma as high risk.

An international collaboration

In the new study, which was actively supported by many international myeloma study groups from Germany, Holland, Italy and Spain and industry partners, the researchers carried out a systematic review of 24 randomised controlled trials of myeloma around the world in which data about HRCAs was included, over a 20-year period. 

They invited the groups involved in those trials to perform an analysis of their data for both single hit (one HRCA) and double hit (two or more HRCAs), using a specially designed algorithm, and to send the individual results back so that they could be jointly studied.

When the teams collated and analysed these results involving in total 13,926 patients, they showed for the first time that patients with two or more HRCAs were 2.28 times (more than twice) as likely to experience early disease progression than the control group (who had no HRCAs), regardless of the specific type of standard care treatment. Those with one HRCA were around 1.51 times more likely to experience early disease progression as the control group.

They also found that patients with two or more HCRAs were 2.94 times more likely to die from the disease early, compared with the control group, while patients with one HRCA were 1.69 times more likely to die early.

Evidence for a personalised approach

Because the project involved many studies over a long time, the researchers could tell that in newer trials, (those performed since 2015), the effect remained consistent. This reinforces that some high-risk patients need better, tailored approaches than current standard therapies.

Evidence that tailored approaches can help patients with ‘double hit’ myeloma live longer was shown in the OPTIMUM MUK 9 trial, co-led by The Institute of Cancer Research (ICR), The University of Leeds and The Royal Marsden NHS Foundation Trust. OPTIMUM MUK 9 was the first trial in the world to use state-of-the-art diagnostics to screen for high-risk myeloma, and to offer personalised treatment for those patients identified to have the greatest need at the same time.

The results of the trial showed that an intensive treatment regime of five drugs along with a stem cell transplant, kept the cancer at bay three times longer and doubled survival time for high-risk patients.

Informing international good practice

The results of the analysis have already informed good practice guidelines for more accurate diagnosis of myeloma patients by the British Society of Haematology and are set to contribute to international reference for genetic testing in myeloma. However, the NHS has yet to adopt the results of the OPTIMUM MUK 9 trial. The trial driven by UK academic researchers, who in partnership with the charity Myeloma UK, recognised the unmet need left unaddressed by standard approaches in daily practice.

The study received funding from Myeloma UK and Cancer Research UK and was supported by funding from the National Institute for Health and Care Research and the British Research Council.

‘Our research highlights critical unmet need in this group of patients’

Study leader Professor Martin Kaiser, Professor in Molecular Haematology at The Institute of Cancer Research, London, and Consultant Haematologist at The Royal Marsden NHS Foundation Trust, said:

 “Myeloma is a very complex cancer. While current treatments can work very well for many people, there are others who do not respond well and may relapse early. 

“Our research highlights the critical unmet need in this group of patients who are not benefiting from current standard treatment for myeloma. We’re aiming to find better ways of treating these patients and improving their outcomes.

“The results of this study have enabled us to more accurately classify the aggressiveness of an individual patient’s cancer. We would like all myeloma patients to be able to access the newer diagnostic tests which enable clinicians to group individual patients based on their risk profile and provide treatment that is tailored to their needs.

“We have already shown through the OPTIMUM trial that a more personalised approach involving five different existing drugs could help treat patients with the highest-risk forms of myeloma – helping keep them alive and healthy for longer.”

Professor David Cairns, Professor of Clinical Trials Research and Deputy Director of the Leeds Cancer Research UK Clinical Trials Unit at The University of Leeds, said:

“This study shows the most convincing evidence yet that multiple genetic abnormalities lead to poor prognosis for all patient groups.

“It was a pleasure to work with academic and industry collaborators from around the world on this federated analysis. The support of Cancer Research UK and Myeloma UK to the Clinical Trials Research Unit at the University of Leeds helped make this project possible." 

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

“Cancer is not a single disease. There are many different types and sub-types of cancer, each with its own characteristics, risk factors and causes. Because of this incredible diversity, it is vital that we can diagnose cancer precisely to identify the best treatment for each patient.

“This study represents an important step forward in better understanding and defining the needs of high-risk multiple myeloma patients. Every cancer patient should have the opportunity for their cancer to be molecularly profiled to assess biomarkers that can give vital clues about how their disease should best be treated. Biomarker tests can tailor treatment precisely to the patients who will most benefit, which can both improve the lives of patients, and increase the cost-effectiveness of treatment for the NHS.”

Shelagh McKinlay, Director of Research and Advocacy at blood cancer charity Myeloma UK, said:

“We’re immensely proud to be funding Professor Kaiser’s work, which is paving the way for a brighter future for people with myeloma.

“We know that, when it comes to treating people, a one-size-fits-all approach doesn’t work for myeloma. Professor Kaiser’s research takes us a major step forward as we strive to identify patients at high risk of not responding to currently available treatments and to develop bespoke treatments that will keep their cancer at bay for as long as possible.

“This work also shows the clear need for greater access to early genetic testing so we can target people’s cancer far more effectively.

"Until we have a cure, it is absolutely vital that myeloma patients are given the best chance to keep their cancer in check, and it starts with making sure they get access to personalised medicine.”

‘I went on the trial because I wanted to help scientists find a cure’

Dorian Burrows,76, lives in Norfolk and was diagnosed with high-risk myeloma in 2019. 

“I’d already been diagnosed with prostate cancer and was being treated on a watch and wait basis. But then I had terrible back pain, and my GP ordered blood tests which revealed myeloma. I was just about to start treatment when I was called in by the consultant who told me that further blood tests had revealed high risk myeloma and I probably had between six months to five years to live.

“He also said if I could get to the Plasma Cell Disorder Clinic at the Norfolk and Norwich Hospital that afternoon, I might be able to get on the MUK9B clinical trial. Entry to the trial was closing that evening. Luckily, I made it in time and was accepted for the trial.

“I have a great family - my wife, two children and four grandchildren. They’ve kept me going through my treatment which has enabled me to carry on with the other great passion in my life - riding motorcycles. When I was diagnosed, I swapped my two-wheel Harley for a three-wheel Can Am Spyder. Last year I did 15,000 miles on it with my friends, the members of the No Rules, Have Fun club we set up together. Having an all-encompassing hobby is so important in keeping a positive attitude to myeloma.

“My treatment on the trial is a tough one, six months of induction treatment followed by an Autologous stem cell transplant which was followed by a 12-month consolidation stage, I am now on part five the maintenance stage. I’ve just celebrated my 42nd month of remission. I’m currently taking the drug Daratumumab monthly.

“It's not a matter of if, but when, my myeloma will come back, but there’s absolutely nothing I can do about it, apart from take the treatments. I went on the trial because I wanted to help the scientists find a cure. I know I’m alive today because of research. I’ve followed the ICR for a while now. I’m so impressed by what they’ve achieved, and I am hopeful that new treatments will be found.”