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 2/2025

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Recent discoveries from this group

05/03/25

Researchers have uncovered several biological signs that may determine how metastatic castration-resistant prostate cancer (mCRPC) responds to a new treatment combination. The scientists made these discoveries as part of a phase III mCRPC trial investigating the effects of adding the drug ipatasertib to abiraterone, the standard of care.

Using a powerful sequencing technique to analyse tumour samples, the team showed that the addition of ipatasertib, an AKT inhibitor, helped certain groups of mCRPC patients – those whose cancer had specific genetic alterations – survive longer without the disease progressing. However, other patients did not benefit.

This knowledge could be used to help ensure that patients who are likely to benefit from the combination therapy receive it while others are spared unnecessary additional medication.

The study findings may also lead to new treatments for prostate cancer, as the identification of tumour genomic alterations associated with greater benefits revealed a biological pathway that researchers are now targeting in drug development work. Better treatment options are urgently needed for this condition, as the aggressive nature of the prostate cancer subtypes with these targeted alterations means that outcomes are generally poor.

Professor Johann de Bono, Head of the Division of Clinical Studies at The Institute of Cancer Research, London, was first author on the paper, which was published in the journal European Urology. The research was funded by Roche.

Outcomes are not consistent across the patient population

The trial, called IPATential150, enrolled 1,101 patients with previously untreated mCRPC. All of the participants received abiraterone, but while half of them received ipatasertib alongside it, the others were given a placebo instead.

Abiraterone, which was designed and developed at The Institute of Cancer Research (ICR), works by stopping the body from making testosterone, which prostate cancer uses to grow. Ipatasertib has a different mode of action, blocking the activity of a protein called AKT to inhibit cell proliferation and migration.

Overall, the addition of ipatasertib to the treatment regimen did not have a significant effect on the participants’ survival. At a median follow-up of 33.9 months, the median overall survival was only slightly longer in the ipatasertib group than in the placebo group – 39.4 months compared with 36.5 months.

However, when the researchers looked more closely at the most common genetic alterations across the patients’ tumour samples, they were able to associate certain characteristics with better or worse outcomes.

The importance of genetics

Of primary interest was the loss of PTEN gene function, which affects almost half of mCRPC patients and can occur due to genomic deletions or rearrangements. This gene suppresses the AKT signalling pathway that is often overactive in prostate cancer. The pathway regulates cell growth, survival and metabolism, and when dysregulated, it can promote the progression of the disease. Given that ipatasertib affects this pathway, the team were keen to see whether its addition to the treatment regimen led to better outcomes for this group of patients.

The researchers also investigated the PIK3CA/AKT1/PTEN pathway, which is known to be a major signalling pathway in multiple types of cancer. It has roles in controlling the survival and spread of cancer, as well as in managing the tumour environment. Analysis of the patients’ tumour samples revealed that the PIK3CA/AKT1/PTEN pathway was altered in 34 per cent of cases.

When the researchers compared the groups of patients with PTEN loss or PIK3CA/AKT1/PTEN pathway alterations with the other participants, they found that the addition of ipatasertib to abiraterone increased median overall survival by a more notable amount – from 29.2 months to 37.1 months.

This suggests that people whose tumours have these characteristics are likely to benefit from the ipatasertib-abiraterone combination treatment. This approach is not yet approved for clinical use, but the current research provides convincing evidence to support its use as a standard of care for certain patients.

Further research on the PIK3CA/AKT1/PTEN could also lead to new targeted medications that improve outcomes for more people with mCRPC.

“There is an urgent need for new treatments that improve outcomes”

Professor Johann de Bono, Regius Professor of Cancer Research and a Professor in Experimental Cancer Medicine at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust, said:

“Many different genes can play a part in the development and progression of mCRPC, and the genetic changes across cells within the same tumour can be very diverse. As a result, patients typically develop treatment-resistant disease that is difficult to treat. There is an urgent need for new treatments that improve outcomes in these aggressive subtypes of prostate cancer.

“We are pleased that this trial – the first phase III trial of an AKT inhibitor, ipatasertib, with abiraterone in this type of prostate cancer – has uncovered new biomarkers that could help identify the patients most likely to benefit from this combination treatment.

“Further trials are needed to identify other groups of patients who may find this approach effective, but based on our findings, we believe that it could benefit about 12,000 people a year in the UK alone. The number of years of life saved could be extraordinary."