The Contribution of Hybrid Photon Counting Detectors to Breast Cancer Research
A 10-minute read
October was Breast Cancer Awareness Month - how do Hybrid Photon Counting detectors contribute to related research, and how is DECTRIS involved?
Breast cancer can affect people of all ages: from older to younger women, and even men, who have or don’t have a family history of the disease. Being aware of it and doing regular examinations can save lives.
Statistics
Breast cancer is a prevalent and life-altering disease that affects millions of individuals worldwide. According to the World Health Organization (WHO), breast cancer is the most common cancer among women, with over 2.3 million new cases diagnosed in 2020. Also, at the end of 2020, 7.8 million women had been diagnosed with the disease within the previous five years; this establishes it as the most widespread cancer globally. Despite the fact that most cases appear in women, it is also worth mentioning that 1% of the cases were found in men, reminding us that breast cancer is not only a women’s affair.
These statistics are staggering, highlighting the urgent need for awareness, early detection, and effective treatment.
Diagnosis and Early Detection
Early diagnosis is paramount in the battle against breast cancer. Regular screening methods, including mammography and clinical breast exams, can help to detect the disease in its early stages, when it’s more treatable.
Even though most countries’ health organizations recommend mammography to people older than 40, another way to identify malignity can be self-breast examinations, which are valuable for detecting lumps or changes in breast tissue. If any abnormalities are found, a healthcare provider may order further tests, such as an ultrasound, MRI, or biopsy, to confirm the diagnosis.
Treatment and Hope for a Cure
Breast cancer is not a single disease but encompasses various subtypes, each requiring tailored treatment approaches.
Targeted therapies have revolutionized treatment. For instance, one subtype of breast cancer is associated with a strongly increased number of so-called HER2 receptor proteins on the surface of cancer cells. This subtype can be treated effectively with medications, including Herceptin, which specifically target the HER2 protein. Hormone therapy, such as tamoxifen or aromatase inhibitors, is utilized to stop or slow the hormone-receptor-positive tumors, or even to shrink them.
The journey from diagnosis to recovery is often complex and can involve surgery, chemotherapy, radiation therapy, or a combination of these. Advances in research and personalized medicine have improved survival rates and the quality of life for many patients. While breast cancer can be a formidable adversary, early diagnosis, access to innovative treatments, and ongoing research offer hope for a cure, as well as better outcomes for those affected.
The suggested treatments and early prevention yield very hopeful results; according to Cancer Research in the UK, 90% of women with the disease will survive their cancer for 5 years after diagnosis. Public awareness, regular screenings, and support for breast cancer research are essential to continued progress in the fight against this disease.
But how do X-ray macromolecular crystallography and DECTRIS detection technology contribute to the fight?
Breast cancer is a complex disease with various subtypes, and its development and progression involve the dysregulation of multiple proteins and genetic factors. Macromolecular crystallography is a method used to determine the three-dimensional atomic structure of molecules, by analyzing their diffraction patterns after exposure to X-rays. Therefore, it is an explicitly important tool for research against breast cancer.
With the development of Hybrid Photon Counting (HPC) detectors, scientists are able to collect excellent-quality data that accelerate discoveries. With these highly sensitive and noise-free X-ray detectors, scientists can now capture even the weakest signal, and this enhances the precision and accuracy of macromolecular structure determination. In the Protein Data Bank, everyone can have free access to macromolecular structures that are related to breast cancer and were identified with data collected using DECTRIS detectors.
Although many proteins are associated with breast cancer, some are particularly noteworthy due to their well-established roles in the disease. Here are a few key proteins and their roles:
Key Proteins in breast cancer research and their roles.
Learn more about the protein functionalities depicted above!
Proteins Used for Cancer Detection:
- BRCA1 and BRCA2 (Breast Cancer Genes 1 and 2): Mutations in these genes are associated with an increased risk of hereditary breast cancer. Genetic testing for BRCA mutations can help to identify individuals who are at a higher risk.
- ER (Estrogen Receptor): The ER status is assessed in cancerous breast tumors to determine if they are hormone-receptor-positive. This information helps to guide treatment decisions.
- PR (Progesterone Receptor): Like the ER status, the PR status is used to classify tumors and guide hormone therapy decisions.
- HER2 (Human Epidermal Growth Factor Receptor 2): Testing for HER2 status helps to determine if a tumor is HER2-positive. This can then inform treatment with HER2-targeted therapies, including Herceptin.
Proteins Targeted for Treatment (Cure):
- HER2: HER2-targeted therapies, such as Herceptin, Perjeta, and Kadcyla, are used to treat HER2-positive breast cancers.
- ER and PR (Estrogen and Progesterone Receptors): Hormone therapies, such as tamoxifen, aromatase inhibitors, and fulvestrant, are used to treat hormone-receptor-positive breast cancers.
- EGFR (Epidermal Growth Factor Receptor): EGFR-targeted therapies may be used in some cases, especially when the EGFR is overexpressed.
- Bcl-2: Although it is not a primary target, some research is being done on enhancing treatment responses in certain breast cancer subtypes.
Proteins Used for Assessing Tumor Characteristics:
- Ki-67: Ki-67 is a marker of cell proliferation. High levels can indicate a more aggressive tumor and may influence treatment decisions.
- p53: Mutations in the p53 protein can be associated with more aggressive forms of breast cancer.
A protein structure complex brings hope for breast cancer treatment
The Human Epidermal Growth Factor Receptor 2 (HER2), a protein that is related to breast cancer, can be used for detecting or treating the disease. Kast et al. have published their research in a Nature Communications article regarding the engineering of an anti-HER2 biparatopic antibody with a multimodal mechanism of action. In this research, the crystal structure HER2-binding scFv-Fab fusion 841 is presented. The data were collected at the Swiss Light Source, using a DECTRIS EIGER X 16M detector with 2.2 Å resolution.
According to the authors, the engineered scFv–Fab 841 can slow the growth of cancer cells. It acts in a similar manner to a special treatment that is designed to target the protein HER2. This hints at the possibility of using 841 as a treatment for cancers that rely on HER2 for their growth!
Once we understand the impact of the breast cancer research that is happening at the molecular level, it is clear that scientists need to have access to the best, high-precision X-ray detectors that can help them “see” the finest signals of their samples.
An example of a protein complex structure related to breast cancer research: HER2-binding scFv-Fab fusion 841 (PDB:6ZQK). The structure was published in a 2021 Nature Communications article by Kast et al.
Conclusion
To conclude, the main ways to diagnose and treat breast cancer are medical and include ultrasound, mammography, and surgery or chemotherapy. However, there is a lot of research happening at the molecular level. By identifying the X-ray structures of the molecules, scientists can diagnose cancer cases, predict the risk of future case, and also design suitable drugs for targeted therapies.
HPC detector technology facilitates this research at the molecular level by enabling scientists to obtain the best possible precision and data resolution. We are very proud that our detectors facilitate this research, and let’s remember that breast cancer awareness is a matter not only for women, but for all of us.
References
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The role of p53 in breast cancer progression: Insight into p53-targeted therapy
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Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action
The figure in this article was created using the PyMOL Molecular Graphics System, Version 1.2r3pre, Schrödinger, LLC.
