Scientific achievements of 2021

September 2020

AI reveals cancer’s evolutionary history

Image: Artificial intelligence graphic from Pixabay. Licensed under a CC 0 Creative Commons license.

Scientists led by Professor Andrea Sottoriva and his Evolutionary Genomics and Modelling Team created a sophisticated computing method that can reconstruct the patchwork of genetic faults within tumours and their evolutionary history during the disease’s development. The new model combines artificial intelligence with the mathematical models of Charles Darwin’s theory of evolution to analyse genetic data. Applying new algorithms to DNA data taken from patient samples revealed that tumours had a simpler genetic structure than previously thought.

At first look, the genome of a cancer can appear very complex, but the new research – which involved the analysis of more than 2,600 tumour samples – shows how this complexity emerges from the combination of a few simple patterns. The discovery gives us a powerful window into the cancer genome and how tumours evolve over time, which could help shape approaches to treatment. 

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October 2020

A blood test can identify different mutations in breast cancer and match patients to treatment

Image: Blood samples. Credit: Ahmad Ardity via Pixabay

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October 2020

New therapy combining inhibitor drugs can treat resistant cancers

Image: Dispensing medicines for a clinical trial. Credit: Jan Chlebik/ICR

A new drug combination can benefit patients by targeting two fundamental weaknesses in cancer at the same time, a new clinical trial has shown. The trial was the first to use the pioneering genetically targeted drug olaparib together with a promising new medicine, called capivasertib. The ICR played a key roles in pioneering both of these precision medicines, collaborating to create a precursor to capivasertib and discovering how to genetically target olaparib. Olaparib targets cancers with damaged systems for DNA repair, while capivasertib blocks a molecule called AKT which fuels tumour growth.

In the trial, led by Professor Johann de Bono, Head of the ICR’s Division of Clinical Studies, 25 of the 56 patients benefited from treatment, with their tumours either shrinking or no longer growing. Some of the patients who benefited from the combination had previously stopped responding to chemotherapy, and may had mutations to genes involved in repairing DNA, including to the BRCA genes. This early clinical evidence shows that olaparib and capivasertib have the potential to work well as a combination treatment and could improve outcomes for some patients with drug-resistant cancer

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November 2020

New drug targeting neuroblastomas ready for clinical trials in children

Image: Neuroblastoma of the adrenal gland. Credit: Ed Uthman. CC BY-NC 2.0

Our researchers found that a new drug that has passed safety tests in adults has the potential to be effective against the aggressive childhood cancer neuroblastoma – and plan to make the drug available to children through a clinical trial. The drug is called fadraciclib and was jointly discovered by scientists at the ICR, in collaboration with the company Cyclacel.

Scientists led by Professor Louis Chesler, who leads the Paediatric Solid Tumour Biology, and Therapeutics Team found that the drug blocks the cancer-driving effects of changes to the N-Myc gene, which occur in aggressive forms of neuroblastoma. Given by itself to mice, the drug slowed down and stabilised tumour growth, and in combination with the chemotherapy drug temozolomide shrank tumours to the point of virtually eradicating them and with a remarkable extension in survival. Fadraciclib is now available to eligible young patients as part of the international ESMART clinical trial, led in the UK at The Royal Marsden’s Oak Centre for Children and Young People.

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November 2020

AI-generated images help to guide radiotherapy

Image: Radiotherapy IMRT. Credit: Jan Chlebik / The ICR

Artificial intelligence could be used to synthesise magnetic resonance images of head and neck cancers from CT scans – as a way of guiding radiotherapy faster and more accurately than is currently possible.

The study led by Professor Uwe Oelfke, Deputy Head of the Division of Radiotherapy and Imaging, showed healthy organs and tumour tissue can be segmented in these images to help guide and deliver radiotherapy in real time. The researchers generated the MRI images from existing CT scans of the salivary glands of people with head and neck cancer.

CT images for radiotherapy are widely available, while MRI may not be. ICR researchers therefore trained AI to produce synthetic, good-quality magnetic resonance images of the patients’ salivary glands, which could then be used to segment tissues of interest. Currently, the segmentation is done manually, which is expensive, time-consuming and subjective. This helps with the problem of data scarcity in medical imaging, and could be used in the clinic to automatically transfer information about one type of image onto a new one using AI, to map out target regions of a patient’s an atom 

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December 2020

New 3D structure could be a treasure map to discover new treatments

Image: RNA Polymerase III. Credit: Alessandro Vannini/Jeroen Claus, Phospho Biomedical Animation

Scientists led by Professor Alessandro Vannini, Deputy Head of the ICR’s Division of Structural Biology, have created a three-dimensional map of a protein complex found in human cells which could be used as a guide to discover new treatments. When this complex mutates, it is linked to increased sensitivity to viral infections and neurodegenerative diseases, and potentially also to cancer. The protein complex, known as RNA polymerase III or Pol III, reads DNA to decode ‘housekeeping’ genes that form the basic building blocks of cells. Cancer cells often hijack this process to fuel their rapid growth and division so this 3D structure could act like a treasure map for guiding future research.

Three years ago, ICR scientists unveiled the structure of Pol III in yeast. Now the same team of scientists working with colleagues in Germany, have revealed the three-dimensional structure of the human version of the protein complex. The team used two Nobel Prize winning techniques in the research– a revolutionary type of microscopy called Cryo-EM and a technology to edit genes known as CRISPR.

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June 2021

Trial shows the benefits of targeted drugs against early-stage breast cancer

Women with high-risk, early-stage breast cancer who also have inherited faults in their BRCA1 or BRCA2 genes had a remarkable response to the targeted drug olaparib in a major clinical trial led. The trial was led internationally by Professor Andrew Tutt OlympiA Steering Committee Chair, Professor of Oncology at the ICR, and King’s College London

Olaparib works by stopping cancer cells from being able to repair their DNA by inhibiting a molecule called PARP. It gets trapped on DNA in a way that makes the cancer cells reliant on the BRCA1 and BRCA2 genes. The cancers then die if there are faults in these genes. Adding olaparib for one year following standard treatment cut the risk of breast cancer returning by 42 per cent.

Women with early-stage breast cancer who have inherited BRCA1 or BRCA2 mutations are typically diagnosed at a younger age. Up to now, there has been no treatment that specifically targets the unique biology of these cancers to reduce the rate of recurrence. The new findings also show the value of testing for inherited BRCA mutations in women with early-stage breast cancer to identify those who could benefit from this new targeted approach.

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June 2021

New drug class could treat range of cancers with faulty BRCA genes

Image: Breast cancer cells. Credit: Min Yu, National Cancer Institute \ USC Norris Comprehensive Cancer Center

Scientists led by Professor Chris Lord, who leads the Gene Function Team, have identified a new class of targeted cancer drugs that offer the potential to treat patients whose tumours have faulty copies of the BRCA genes. The drugs, known as POLQ inhibitors, specifically kill cancer cells with mutations in the BRCA genes while leaving healthy cells unharmed. This class of drugs can kill cancer cells that have become resistant to existing treatments for patients with BRCA mutations.

POLQ inhibitors could enter the clinic as a new approach to treating a range of cancers with BRCA mutations, such as breast, ovarian, prostate and pancreatic cancer. Genetically removing a protein known as POLQ destroys cells with BRCA gene defects, but drugs that prevent POLQ from working had not been identified until now.

New POLQ inhibitors could provide a new approach to treating cancers with BRCA gene defects, on top of existing PARP inhibitors. This is important since POLQ inhibitors should retain their activity in cancers that have developed resistance to PARP inhibitors, giving patients more options for treatment.

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June 2021

Key genetic changes underlie the development of rhabdomyosarcoma in children

Image: Rhabdomyosarcoma cells. Credit: Dr Ewa Aladowicz, ICR

The largest and most comprehensive study in rhabdomyosarcoma revealed key genetic changes underlying development of the disease. The study, led by Professor Janet Shipley, Head of the Division of Molecular Pathology at the ICR, found these specific genetic changes in tumours were linked to aggressiveness, early age of onset and location in the body.

By looking at the genetic features of different tumours, scientists could divide children into different risk groups to help guide their treatment. Rhabdomyosarcoma is a rare type of cancer that resembles muscle tissue and mostly affects children. Less than 30 per cent of children with rhabdomyosarcoma who have relapsed or whose cancer has spread will survive.

There are two main subtypes – fusion gene-positive and fusion gene-negative– depending on whether a hybrid gene is present formed from two previously separate genes. Researchers found that children with fusion-negative rhabdomyosarcoma whose tumours had faults in two particular genes, MYOD1 and TP53, had significantly poorer outcomes than those without these genes. Scientists made the findings after analysing DNA from 641 patients with rhabdomyosarcoma

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July 2021

Important protein process recreated in the test tube provides clues to bowel cancer

Image: Test tubes. Credit: Jan Chlebik / The ICR

Scientists led by Dr Sebastian Guettler, Deputy Head of the ICR’s Division of Structural Biology, recreated a key cellular signalling system within a test tube– providing important clues to what goes wrong when cancer develops.

The researchers reconstructed an assembly of proteins known as the ß-catenin destruction complex. Mutations in this destruction complex are found in a large percentage of bowel and other cancers, and scientists have been keen to understand their role in promoting cancer. By reconstructing the destruction complex, the team gained detailed insights into how two key genes function in keeping ß-catenin levels constant.

The researchers also investigated how this process goes awry in cancer. ß-catenin is constantly created and destroyed in a natural cycle, so the overall amount available in the cells is kept low. However, mutations in ß-catenin itself can cause it to skip the destruction part of this cycle. Ultimately this tells the cell to keep dividing uncontrollably – which leads to cancer. There are currently no cancer drugs in the clinic that target the Wnt/ß-catenin pathway, but the new research could help in opening up new approaches to treatment

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