Potential for SCLC Blood Test unlocked by Manchester University
A transatlantic study, led by CRUK Manchester Institute Cancer Biomarker Centre researchers based at the city’s university, along with a team at Memorial Sloan Kettering Cancer Center in New York, could pave the way for diagnosing and characterising early stage small cell lung cancer (SCLC) using a simple blood test.
The research team has developed a method sensitive enough to detect specific DNA modifications (methylation) in the very low levels of DNA shed from a patient’s tumour into the blood stream, known as circulating tumour DNA (ctDNA). The test was sufficiently sensitive and accurate to detect methylation of ctDNA, even from patients whose tumours were diagnosed at the earliest stage. A computational method to assess which methylation modifications were present has also been developed.
While the standard treatment for SCLC is chemotherapy, recent studies suggest that multiple types of this aggressive form of cancer might respond differently to a range of therapies. The new blood test was also able to classify which type of SCLC is affecting a patient, supporting the potential for more personalised treatment options.
Professor Caroline Dive who led the study commented: “SCLC is a terrible disease, causing so much anguish to patients and
Professor Caroline Dive
their families. We think this blood test could be really useful in future clinical trials of new therapies to predict and monitor treatment responses.”
Dr Dominic Rothwell, who headed the laboratory work said: “A key advantage of blood-based molecular subtyping is that blood is much easier to collect and is able to circumvent the challenges often encountered in analysing scant and often extensively necrotic tissue associated with tumour biopsies. Our study opens up the exciting possibility of detecting SCLC earlier and assigning patients to more
Professor Charles Rudin personalised treatments.”
Professor Charles Rudin, Chief of Thoracic Oncology at Memorial Sloane Kettering Cancer Center, leads the global consortium that defined the different types of SCLC: “To our knowledge, this is the first published study to show that DNA methylation analysis of a blood sample can identify the SCLC molecular subtypes. Though further validation is clearly now needed in a larger independent patient cohort, this blood test could one day assist clinicians in choosing better treatments for SCLC, which is currently notoriously difficult to manage.”
Dr Dominic Rothwell
Dr Marianne Baker, Research Information Manager at Cancer Research UK which funded the study said: “These promising early results show that the CRUK Cancer Biomarker Centre is leading the way in developing liquid biopsies. These could allow doctors to spot a person’s lung cancer earlier and even track how a cancer changes over time, helping them to choose the best treatments.”
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Key Biomarkers for Prediction Response to Melanoma Therapy identified
Using advanced computing technology scientists at the Wistar Institute have been able to provide evidence of novel, reliable biomarkers that better predict therapy response of patients undergoing immune checkpoint inhibitor (ICI) treatment. ICI therapy, a type of treatment for melanoma (skin cancer) blocks proteins on tumour or immune cells that prevent the immune system from killing cancer cells. While this treatment has shown some clinical success in patients with advanced stages of melanoma, its efficacy depends on reliable predictors of a patient’s response to the therapy. Currently, the only FDA approved biomarker for ICI melanoma treatment is the tumour mutation burden assay, but the mechanisms linking it to ICI remain unclear.
Noam Auslander, Assistant Professor in the Molecular & Cellular Oncogenesis Program of Wistar’s Ellen and Ronald Caplan Cancer Centre and Andrew Patterson, graduate student in the Auslander lab, have now identified novel predictors of ICI therapy for melanoma. In particular,
mutations in the processes of leukocyte and T-cell proliferation regulation show potential as biomarkers with reliable and stable prediction of ICI therapy response across multiple different datasets of melanoma patients.
“This work aims to identify better and more biologically interpretable genomic predictors for immunotherapy responses,” noted Auslander. “We need better biomarkers to help select patients that are more likely to respond to ICI therapy and understand what factors can help to enhance responses and increase those numbers.”
Using publicly available de-identified clinical data, researchers investigated why some melanoma patients responded to ICI therapy and others did not. Patterson, first author on the paper, detailed that their research process involved training machine learning models on a dataset to predict whether a patient responds to ICI therapy, then confirming that the model was able to continually predict response or resistance to this treatment over multiple other datasets.
The team found that leukocyte and T-cell proliferation regulation processes have some mutated genes that contribute to ICI treatment response and resistance. This knowledge could be used to identify targets to enhance responses or mitigate resistance in patients with melanoma.
“We were able to better predict if a patient would respond to ICI therapy than the current clinical standard method as well as extract biological information that could help in further understanding the mechanisms behind ICI therapy response and resistance,” Patterson explained.
The paper was published in Nature communications More information online:
ilmt.co/PL/4Eyx
Noam Auslander
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The Eppendorf Award for Young European Investigators, endowed with €20,000, is granted annually to an early career scientist in Europe for outstanding contributions to biomedical research. It has been awarded, in partnership with Nature, since 1995.
Researchers in Europe up to 35 years of age with an advanced degree in the field of biomedical research can apply only between 1 October 2022, and 15 January 2023.
The winner is selected by an independent expert committee chaired by Reinhard Jahn (Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany).
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Eppendorf Young European Investigators Award 2023: Call for Entries
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