Breast cancer is the more prevalent cancer in women. Please share the initiatives by Agilent towards better cancer diagnostics.
In 2020, there were 2.3 million women diagnosed with breast cancer and 685,000 deaths globallyi. Breast cancer accounts for 14% of cancers in Indian womenii. Improving the diagnosis of breast cancer is one of the key priorities for Agilent within its diagnostics and genomics business area. In 1998, Agilent Dako in collaboration with Genentech launched the first companion diagnostic test for breast cancer. The HercepTest is still routinely used to test patients for whom treatment with Herceptin is being considered.
Cancer is a complex disease that can be attributed to many factors and requires different technologies to correctly diagnose. Agilent’s broad portfolio includes genomics tools, next-generation sequencing (NGS) solutions, Dako companion diagnostics and pathology solutions along with liquid and gas chromatography, mass spectrometry, spectroscopy, and cell analysis platforms are the cornerstone to this fight. Our workflow combining metabolomics and cell-based tools with more efficient CRISPR-based engineering of T-cells allow labs to validate and maintain quality control downstream in development and manufacturing. Our bioinformatics tools and databases are also key in the study of cancer.
We collaborate with a global community of cancer researchers that help us understand the disease betteriii. We then turn this knowledge into insights that translate into better diagnostic tools for our customers. For example, our NGS panels for somatic cancer biomarker profiling were designed by our clinical cancer research experts for detecting genetic variants and genomic signatures. Another example is of our NGS panel of 151 key genes associated with a wide range of cancers, including breast, lung, colorectal, and acute myeloid leukemia (AML) developed in collaboration with cancer researchers from Washington University in St Louis. Along with working with top academia experts, Agilent also partners with top-tier pharmaceutical companies to develop diagnostic tests for cancer therapy.
The Agilent Thought Leader Award (TLA) program promotes fundamental scientific advances by contributing financial support, products, and expertise to the research of influential thought leaders in the life sciences, diagnostics, and chemical analysis space. Agilent recently presented TLAs to two prominent researchers in the field of CAR T-cell mediated cancer immunotherapy to “define standards for the design, validation, and manufacturing of cell-based cancer therapeutics”iv.
How are Agilent’s pathological solutions addressing today’s cancer challenges and how does it define the treatment of breast cancer?
We are constantly enhancing our pathological solutions portfolio with new generations of clinically relevant products. Agilent is a provider of complete pathology solutions and flow cytometry reagents and is a trusted partner of clinical laboratories across the globe. Agilent Dako has a very broad portfolio comprising of immunohistochemistry (IHC) solutions, special stains solutions, hematoxylin & eosin (H&E) and molecular florescence in situ hybridization/in situ hybridization (FISH/ISH) solutions. To address the high-throughput demand of most pathological testing laboratories, we have developed automation tools. This has vastly improved workload management and report generation while maintaining optimal IHC staining results. For example, Dako Omnis enables automation of advanced staining techniques, while using the simplest of user interfaces with little hands-on time. All these solutions encompass breast cancer along with a repertoire of other cancers.We also recognize that the role of pathologists is immense when it comes to diagnostics and that they should be equipped with the very latest knowledge. Our engagement with global leaders helps to disseminate knowledge about testing guidelines and recent advances by bringing together pathologists and the KOLs in one common forum, ensuring that the experience is shared across the pathology community. Agilent conducts educational symposiums at various conferences that bring together pathologists and lab staff to hear top experts in cancer diagnosis share their perspectives.
We also conduct regular comprehensive webinars and interactive e-learning programs inviting pathologists. These events help pathologists stay current with new assays, helping laboratories maintain reporting of high-quality results for the treating physician.
There is an increased focus on personalised treatment. How likely do you think truly personalised medicine is for breast cancer?
Breast cancer has different molecular classes and based on the category, it has different resistant factors and target therapies. Hence, it is vital to have precise genetic profiling of tumours to develop targeted therapies included in an effective drug regimen.
The predominant type of breast cancer is caused by the expression of human epidermal growth factor receptor 2 (HER2) which enhances the proliferation of breast cancer cells. This type of breast cancer is often more aggressive than other types. There are a group of drugs such as trastuzumab that are effective against this type.
Also, there are hormone receptor positive breast cancers and triple negative breast cancers, the latter contributing to approximately 15% of invasive breast cancersv. Triple-negative breast cancer is also more common in women with a mutation in the BRCA1 gene. The treatment regime of these different types of breast cancer will differ based on the type of mutation the women possess. Hence it is highly important to know the genetic profile of these cancers for the clinicians to recommend appropriate drug regimens. Personalized medicine is thus pivotal to this clinical decision-making process.
The area of personalized medicine also demands a need for the identification of new and correct cancer biomarkers, as well as for understanding sample stratification, drug response, etc. Agilent is working with leading researchers globally not only on its genomics platform but also on mass spectrometry-based metabolomics and proteomics tools that have become essential techniques for identifying new biomarkers.
What research projects are you currently working on?
Globally, several cancer projects are currently underway at Agilent. For example, we are working with Baylor College of Medicine for better characterization of prostate cancer.
In India, one project worth mentioning is our collaboration with Narayana Nethralaya, a multi-specialty hospital in Bangalore that specializes in treating eye disordersvi. The main goal of this project is to create a complete profile of a pediatric eye cancer called retinoblastoma. While there has been research into the biological mechanisms and genetic changes behind retinoblastoma, doctors still lack clear and specific progression markers for this cancer. Using tissue and tear samples from patients, we undertook an integrated, multidisciplinary approach co-relating data from genomics, transcriptomics, metabolomics, and proteomics. We leveraged Agilent’s broad range of products and solutions, including microarray scanners, liquid and gas chromatography mass spectrometry systems, state-of-the-art software and database libraries. These diverse technologies enabled us to examine retinoblastoma at its different stages and assemble a complete profile at a metabolite, protein, gene, DNA, and RNA level. This integrated data was then analyzed using Agilent’s GeneSpring suite of bioinformatics software that helped us to gain a deeper understanding of the mechanisms and pathways leading to this disease. We were able to identify new mechanisms and predict potential biomarkers associated with the aggressiveness of cancer – a critical requirement for improved management and treatment of the disease. This research demonstrates the benefit of applying an integrated approach to studying the molecular mechanisms of this disease. The ultimate goal is to give children a better outcome of this disease.
How is Agilent driving the future of precision cancer diagnostics?
Precision medicine is revolutionizing therapy selection for oncology patients as it helps in pairing the right treatment with the right patient. As the first company to achieve FDA approval for a companion diagnostic (CDx) test more than 20 years ago with HercepTest for immunohistochemical determination of HER2 protein expression, Agilent has developed multiple CDx solutions driving innovation and shaping the future of precision cancer diagnostics. To date, Agilent has developed seven FDA-approved PD-L1 indications and is a partner to leading pharma companies and precision drug programs.
Agilent provides support at all stages of development, including coordinating the development of clinical diagnostics from discovery through to clinical trials and registrations to global manufacturing and commercialization. Agilent’s portfolio enables us to accurately guide our partners in pairing the right detection technology with each biomarker target. Our recent acquisition of Resolution Bioscience has added a non-invasive NGS-based liquid biopsy platform to the expansive portfolio, enabling our customers and collaborators to detect all four major types of genetic alterations known to drive cancers.
Role of AI/ML/Blockchain in the diagnosis of breast cancer?
Artificial intelligence (AI) and machine learning (ML) hold great promise in early cancer diagnosis and prediction and are expected to bring a paradigm shift in clinical decision-making. Cancer is a complex disease caused by various genetic and epigenetic variations. AI will be instrumental in identifying these aberrations very early on, enabling cancer prediction and diagnosis through already established techniques like NGS and high-resolution imaging techniques. Leading global institutes, like MIT are making significant progress in developing AI tools to predict breast cancer risk from mammogram imagesvii. While the study showed significant promise, researchers say that the models needed both algorithmic improvements and large-scale validation across several hospitals to prove their robustness.
AI and ML are the future of clinical diagnosis, and as we transition to this technology, the focus will be on bringing it to clinics in a safe and ethical manner. This is reflected in India by increased research funding in big data and genomics. Given the need to identify patterns in data that will enable the transformation of big data into clinically actionable knowledge, these areas are gradually becoming recognized. Though we must remain disciplined in building robust databases in India to enable AI transformation, it will be useful in clinical decision-making throughout the patient care journey, from prediction to prognosis evaluation, early detection, diagnosis, and treatment.
References:
i Breast cancer (who.int)
ii Statistics of Breast Cancer In India | Cytecare Hospitals
iii New discoveries in cancer research | Agilent
ivAgilent Presents Thought Leader Award to Drs. Carl H. June and Michael Milone
vTriple negative breast cancer | Cancer Research UK
vi 5991-6215EN.pdf (agilent.com)
viiRobust artificial intelligence tools to predict future cancer | MIT News | Massachusetts Institute of Technology