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By promoting research and raising awareness, World Cancer Day supporters are working towards a world where everyone gets the cancer prevention, treatment and care they need. Cancer is the second-leading cause of death worldwide, with an estimated 19.3 million new cases and 10 million deaths from cancer in 2020. The number of new cases is expected to rise to 30 million by 2040.
Today we celebrate the role Diamond plays, working with our user community, in pioneering research in this challenging area – from developing new cancer therapies to gaining insights into how cancer cells work. Over 1000 papers using Diamond data were published in 2023, around 10% of which focused on cancer. Here is an update on just some of the cancer studies published from Diamond science in the last 12 months.
Ductal carcinoma in situ (DCIS) is the presence of abnormal but non-invasive cells in the breast milk ducts. DCIS only becomes invasive breast cancer in a small number of cases, but as this cannot currently be predicted, treatment is generally recommended for all cases. The PRECISION team, supported by Cancer Research UK and the Dutch Cancer Society, is working on ways to tell which patients require treatment and those for whom an active-monitoring approach is a better option.
During a recent study led by Professor Keith Rogers of Cranfield University, the PRECISION team used X-ray diffraction on Diamond’s I18 beamline, alongside electron microscopy, to analyse small deposits of calcium that occur in most DCIS cases. They found significant differences in the size, crystallographic features, and chemistry of these microcalcifications, and hope they could be used as biomarkers to complement existing analyses of breast mammograms in the future.
Cancer cells use various strategies to avoid detection and destruction by the human immune system. One of these involves releasing molecules that inhibit the function of immune cells, such as T-cells, that play a crucial role in recognising and eliminating abnormal cells. Studies show that the amino acid L-kynurenine (LKU) plays a crucial role in immune evasion in a wide range of cancers, however, how L-kynurenine suppresses T-cells remains unclear.
An international team of researchers used studies conducted on Diamond’s B23 Circular Dichroism beamline to explore the biochemical mechanisms underlying the suppression of T cell function by L-kynurenine. They reported, for the first time, that L-kynurenine suppresses T cell function as an aryl hydrocarbon receptor (AhR) ligand. Based on their findings, the team proposed a map of the immune evasion machinery involving L-kynurenine, operated by cancers such as metastatic breast cancer. Their work offers potential drug targets for new therapies for these diseases.
Selenium is fundamental to human health, and studies show that it could both prevent and treat cancer. However, the toxicity of its soluble form limits its use as an anticancer agent. An international team of researchers used state-of-the-art techniques to investigate the low toxicity and potential therapeutic properties of selenium nanoparticles (SeNPs) in tests on prostate cancer cells. As selenium is extremely diluted in the biological environment, they required high-performance techniques with a very low detection limit and high spatial resolution for intracellular imaging and used cryopreparation to preserve the chemical and structural integrity of the cells.
X-ray fluorescence (XRF) elemental mapping at Diamond’s hard X-ray Nanoprobe beamline, I14, combined with complementary measurements at the hard X-ray cryo-nanoprobe ID16A beamline at ESRF (Grenoble, France), enabled imaging of the distribution of selenium within treated prostate cancer cells. The results reveal differences in the uptake and localisation of SeNPs capped with bovine serum albumin (BSA), a highly water-soluble and abundant carrier protein of blood plasma, compared to SeNPs capped with chitosan (a non-toxic polysaccharide). The nano-imaging results were combined with other techniques and show BSA capped SeNPs slowed the migration of aggressive prostate cancer cells, offering new insights into the toxicity of SeNPs.
The BRCA1 or BRCA2 genes are important for DNA repair, and inheritable mutations in these genes can increase an individual’s risk of developing breast, ovarian and prostate cancer. PARP inhibitors block a backup repair mechanism, preventing cancer cells from repairing breaks in their DNA and stopping tumours from growing. However, over time, tumours can develop resistance to PARP inhibition and growth can recur. To ensure treatment is effective, researchers need to find ways to kill cancer cells before they develop resistance or to re-sensitise them to treatments.
One option is to develop new drugs that target the human nucleotide glycosidase DNPH1. Researchers from The Francis Crick Institute in London used X-ray diffraction on Diamond’s I03 beamline to determine the crystallographic structures of dimeric human DNPH1 bound to its substrate hydroxymethyl deoxyuridine monophosphate (hmdUMP), at two key stages of the catalytic cycle. Combined with substrate turnover assays, the structures reveal important insights, providing two alternative starting points for rational drug design.
The KRAS gene provides instructions for making a protein (K-Ras) that relays signals from outside the cell to the cell's nucleus, instructing the cell to grow and divide or to take on specialised functions. Mutations in the KRAS gene, which can lead to the overactivation of the KRAS protein and uncontrolled cell proliferation, are found in various cancers, including colorectal, pancreatic, and lung cancers. Although researchers are interested in developing KRAS inhibitors as potential cancer therapies, this has historically proved challenging.
Researchers from AstraZeneca in Cambridge used Macromolecular Crystallography (MX) on Diamond’s I04 beamline as part of a structure-based drug design approach leading to the identification of AZD4747, a potential KRAS inhibitor. Their results suggest that AZD4747 can cross the blood-brain barrier (BBB), offering the potential to treat patients in which cancer has spread from the original (primary) tumour to the central nervous system (CNS).
Many other cancer research projects are taking place at Diamond. We are proud to support the aims of World Cancer Day and to play our part in tackling cancer and changing lives for the better.
World Cancer Day takes place every year on 4 February to unite the world in the fight against cancer. www.worldcancerday.org
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