Celebrating World Cancer Day

Even with significant global progress in diagnosis and treatment, cancer continues to be the leading cause of death worldwide, accounting for nearly 10 million deaths every year. Diamond is proud to be supporting World Cancer Day and its aim to raise the awareness of cancer, encourage its prevention and mobilise action to address the global cancer pandemic.  

Diamond remains at the forefront of cancer research, working to create a future where cancer is no longer a life-threatening disease. The valuable information gathered from experiments conducted at Diamond leads to advancements in the diagnosis and treatment of different cancers. Since Diamond became operational, over 700 papers have cited cancer research, and over 85% of this information is open access, ensuring the data gathered on our instruments is shared - an ideal that is core to Diamond’s purpose to advance knowledge and collaboration in all areas of scientific discovery. 

The following is just some of the recent cancer research activity at Diamond Ligh Source. 

In 2024, Diamond established a drug discovery partnership with Cancer Research Horizons, the innovation arm of Cancer Research UK. The aim is to build a fragment-based drug discovery programme. Cancer Research Horizons has already been using Diamond’s beamlines and XChem facility for fragment-based screening, a technique that involves identifying small chemical fragments that bind to a target protein. These fragments are usually simpler and smaller than traditional drug molecules.

Once they are identified, these fragments can be chemically modified and combined to create more powerful and effective drug candidates. The new partnership aims to enhance this existing collaboration and intends to speed up the drug discovery process, bringing new cancer treatments to patients more quickly. You can read more about the news story at Cancer Research Horizons and Diamond Light Source establish drug discovery partnership.

In the 1960s, scientists discovered bleomycin, a molecule with anticancer properties, while screening bacterial compounds. This drug, used to treat various tumours, works by breaking DNA in cancer cells. However, its interaction with plasma proteins in the bloodstream is less understood. Researchers at the B23 beamline, led by Rohanah Hussain, used synchrotron radiation and circular dichroism to study how bleomycin binds to plasma proteins. 

They found that bleomycin binds strongly to α1-acid glycoprotein (AGP), a protein elevated in cancer patients, potentially reducing the drug's effectiveness. Further analysis showed that the A2 variant of bleomycin binds more tightly to AGP than to human serum albumin (HSA). These findings suggest that adjusting the ratio of bleomycin variants could potentially improve its therapeutic benefit. Moving forward, the team at B23 aim to study whether bleomycin binds to haemoglobin, the blood protein that transports oxygen around the body, and whether this interaction could be linked to lung damage in patients receiving bleomycin. 

Read more in the full science highlight Bleomycin: cancer drug with a hidden flaw. You can also read the original publication, Interaction of Blenoxane and Congeners Bleomycins A2 and B2 with Human Plasma Proteins Using Circular Dichroism Spectroscopy, in the International Journal of Molecular Sciences. 

The protein tankyrase forms punctate structures in cells.

Tankyrase is a crucial protein involved in cancer, diabetes, neurodegeneration, and fibrosis. It supports Wnt signalling, essential for cell division, development, and stem cell maintenance, and controls other cancer-related functions like telomere maintenance. Due to its significant role, tankyrase is a potential drug target. 

Researchers used cryo-electron microscopy at eBIC to study tankyrase's structure and function. They discovered that tankyrase self-assembles into double helix filaments, which regulate its catalytic activity through a polymerisation-induced allosteric switch. This mechanism is similar to the activation of PARP1, another protein in the same family. Despite previous attempts to develop tankyrase inhibitors for cancer treatment, particularly for bowel cancer, side effects have hindered clinical trials. This new understanding of tankyrase's structure and function could lead to the development of more effective and safer inhibitors. 

Read more in the full science highlight Understanding a protein that fuels bowel cancer. You can also read the original publication, Structural basis of tankyrase activation by polymerization, in Nature. 

Osteosarcoma, a cancer primarily affecting children and adolescents, has a poor prognosis and urgently requires more effective chemotherapy strategies. Currently, high-grade osteosarcoma is treated with cisplatin, a DNA-damaging agent introduced in the late 1960s. However, its effectiveness is limited by low bioavailability, toxicity, and acquired resistance. Understanding cisplatin's biological impact at cellular and subcellular levels is crucial for improving its efficacy. 

Previous studies using various spectroscopic techniques provided insights into cisplatin's metabolic effects and cellular responses but did not reveal its impact on specific subcellular regions. The current study employs SR nano-FTIR, a novel method, to probe cisplatin's effects within human osteosarcoma cells at a high resolution. This approach, used on the B22 MIRIAM beamline, aims to enhance the understanding of cisplatin's cytotoxic pathways and foster the development of new metal-based chemotherapeutic agents. 

IR Nanospectroscopy (nano-FTIR) combines s-SNOM with infrared illumination and FTIR-based spectral detection, offering high spatial resolution and label-free chemical analysis. When coupled with synchrotron IR radiation, it becomes a powerful tool for in situ spectroscopy and mapping of cellular constituents, monitoring drug distribution, and drug-biomolecule interactions. This study's findings are expected to contribute significantly to the development of more effective treatments for osteosarcoma. 

You can read the original publication, Synchrotron nano-FTIR spectroscopy for probing anticancer drugs at subcellular scale, in Nature.