Supporting World Cancer Day 2018
Diamond is proud to be supporting World Cancer Day and highlighting our role, working with our user community, in pioneering synchrotron research in every area of cancer – from developing a better understanding of how cancer cells work to delivering new cancer therapies.
Despite major advances in diagnosis and treatment, cancer still claims the lives of 8.8 million people every year around the world. About 4 million of these die prematurely (under the age of 70). World Cancer Day aims to raise the awareness of cancer and its treatment around the world. With the tagline ‘We can. I can.’, World Cancer Day is exploring how everyone can play their part in reducing the global burden of cancer.
Diamond has published over 900 publications in the last 12 months, with around 10% of these focusing on cancer. The wide-ranging research currently covers at least 12 cancer types, with many more general studies on the structure of cancer cells and pathways, potential drug targets and possible drug candidates. Building on last year’s review of some of the key studies in cancer that have taken place at Diamond, here is an update on studies that have been published in the last 12 months.
Understanding cancer cell structure and function: basic research
One of the main areas of basic research is improving our understanding of cancer cell structure and function. Over 30 papers were published last year, including studies providing insights into the enzymes required for DNA repair and a number of biochemical processes involved in cancer initiation, growth and spread. Protein crystallography, molecular modelling and other techniques allow the identification and study of potential drug binding sites, leading to structure-guided drug discovery. Promising cancer drug targets that have been studied over the past year include:
• The bromodomain and extra-terminal domain (BET) family of proteins
• Cyclin-dependent kinases (CDKs)
• CAM4066 (a selective CK2α inhibitor)
• JmjC histone demethylases (KDMs)
• Mcl-1 (a pro-apoptotic BH3 protein family member).
These ongoing studies will provide researchers with the scientific foundations to design new targeted therapies for a wide variety of cancers.
Breakthroughs in the treatment of leukaemia
Acute lymphoblastic leukaemia (ALL) is a rapidly progressing blood cancer that is typically fatal within months if left untreated. Among the drugs currently used to treat ALL are enzymes called asparaginases, which are derived from bacteria. While healthy human cells can make the amino acid asparagine, ALL cells cannot. Asparaginase enzymes are catalysts, helping to break down asparagine to make it unavailable to ALL cells, which then die. A joint UK/Pakistan study described the structure and function of a new asparaginase isolated from the micro-organism Thermococcus kodakarensis. Thermococcus of bacteria live near hydrothermal vents under the ocean and in hot sulphur springs, and this particular species was discovered thriving in a Japanese volcano. Understanding its structure is a vital first step in investigating its suitability as a treatment for ALL and its use as a biosensor to monitor asparagine levels in ALL patients.
A new therapy for breast cancer
A 2017 study using macromolecular crystallography data from Diamond’s I04 beamline has provided detailed insights into buparlisib (BKM120), an experimental treatment for HR+/HER2 breast cancer (the most common form, accounting for more than 70% of breast cancers). The results provide a sound scientific basis for the development of safer drugs that are flexible enough for use as part of a combination of therapies.
Characterising potential new therapies for myeloma
Myeloma is a cancer that develops in plasma cells, which are made in bone marrow. Myeloma can affect many bones in the body and is a relapsing-remitting disease that typically has periods of symptoms requiring treatment followed by periods of remission with no symptoms.
The KDM5 family of enzymes is known to play a pivotal role in the control of cell proliferation and differentiation, both during normal development and in pathological conditions such as cancer. One of these enzymes, KDM5B, is linked to skin, breast and testicular cancers and to poorer survival rates in myeloma.
A University of Oxford study characterised the biochemical and molecular features of KDOAM-25, an inhibitor of KDM5 enzymes. A study using protein crystallization, collection of X-ray data and structure determination at Diamond found that KDOAM-25 could have a potential application as a myeloma therapy. Further studies are required to follow up on this exciting development.
Designing new diagnostic tools and treatments for prostate cancer
Prostate cancer is the most common cancer in men, with over 40,000 new cases diagnosed in the UK each year. Intensive efforts are ongoing to improve early diagnosis of the condition and to develop new therapies.