NCI Center for Cancer Research’s Post

Our recent collaborative study published in Signal Transduction and Targeted Therapy showcases how the AmoyDx® Master Panel provided crucial genomic insights, identifying the potential role of KMT2D mutations in treatment resistance for patients with extensive-stage small cell lung cancer (ES-SCLC). Led by Dr. Zhehai Wang from Shandong Cancer Hospital and Institute, the study evaluated the efficacy and safety of combining sintilimab, anlotinib, and chemotherapy as a second-line or later therapy for relapsed ES-SCLC patients. Through the analysis of circulating tumor DNA (ctDNA) using the AmoyDx® Master Panel, the researchers found that a low blood tumor mutation burden (bTMB) was associated with better clinical outcomes, while KMT2D mutations were linked to primary resistance to therapy. The study also explored how KMT2D mutations affect epigenetic modifications and immune evasion, offering new insights for future therapeutic approaches. We’re proud to have contributed to this significant advancement in cancer research.🔬 🔗 Read the full study here: https://lnkd.in/gwJ5v5tS 🌐 Learn more about the AmoyDx® Master Panel: https://lnkd.in/gqNDCbNW #PrecisionOncology #SCLC #CancerResearch #Biomarkers #AmoyDx #GenomicInsights #KMT2D #Immunotherapy #ctDNA #LungCancer #CancerTreatment

Checkpoint inhibitor resistance! A very informative observation of a CD274 (PDL1) 3'UTR genomic abnormality which developed after therapy with #PDL1 inhibitor #atezolizumab. 3'UTR abnormalities in CD274 drive over-expression of PDL1 which likely contributed to tumour cell survival in this patient as a novel mechanism of resistance... (and also possibly a resistance mechanism that would be restricted to inhibiting the tumour (PDL1) side of the immune synapse? (as opposed to the more commonly used #PD1 blockers..)) Also in the report lots of contributions of genomics and #NGS to making an accurate diagnosis in blood cancer (including #WGS done by Sean Grimmond at Collaborative Centre for Genomic Cancer Medicine). Well done to Dr. Sam Grigg and all involved for getting this important description out there. https://lnkd.in/gDY5VjVp #PrecisionDiagnostics #WilsonCentreforBloodCancerGenomics #hemepath Peter MacCallum Cancer Centre Michael Dickinson Georgie Ryland Stephen Lade

A recent article published in Talanta presents a groundbreaking advancement in the realm of biochemistry: a DNA logic nanomachine designed for the precise identification of multiple microRNAs in tumour cells. This innovative approach leverages the inherent properties of DNA to perform complex logic operations, enabling the detection of specific biomolecules that are often involved in cancer diagnostics. The authors articulate how this technology enhances the sensitivity and specificity of microRNA detection, which is crucial for early cancer diagnosis and personalised medicine. The mechanistic study behind the DNA-based nanomachine showcases its potential not only to improve diagnostic accuracy but also to allow for real-time monitoring of disease progression. One of the standout features of this research is its potential to transform the landscape of cancer diagnostics. By enabling clinicians to discern subtle changes in microRNA profiles, this tool could facilitate earlier intervention strategies and more tailored treatment options for patients. As we continue to grapple with the complexities of cancer, innovations like this provide hope for more effective and personalised therapeutic approaches. The implications of such advancements are significant, paving the way for improved health outcomes and fostering a more informed public about the importance of early detection in cancer treatment. To read more about this important research, visit the full article here: [DNA logic nanomachine for the accurate identification of multiple microRNAs in tumor cells](https://lnkd.in/dbtYiwC6,. #cancer #biochemistry #DNA #microRNA #chemistry #research #healthcare #innovation, If you want to know more about #analyticalchemistry news, follow me: https://lnkd.in/d29pbjb9

As 2024 comes to a close, it surely has brought some wonderful highlights for us. Our review article titled, "Emerging role of EZH2 in solid tumor metastasis," has been published in Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. While the involvement of EZH2 in liquid cancers and tumorigenesis of solid tumors is well-documented, its role in solid tumour metastasis has remained surprisingly scarce in the literature. Our review brings this critical facet to light, building on our own observations published in Nature Communications in 2022, as well as insights from other pioneering studies in the field. We delve into EZH2’s diverse mechanisms, including its methyltransferase-dependent and independent functions, as well as its unique cytoplasmic interactions. We also discuss the functional dichotomy of EZH2 catalytic function and its non-uniform implications on gene expression. The ongoing clinical trials of EZH2 inhibitors for solid tumors further highlight its functional significance and potential impact in cancer therapy. As an equal first author, I am immensely grateful to my co-authors, ayushi verma & SAUMYA RANJAN SATRUSAL , and my mentor Dr.Dipak Datta for their contributions and support in making this work possible. Read the full article here: https://lnkd.in/gqN6hka8 We hope this review will stimulate meaningful discussions and collaborations in understanding and targeting EZH2 in the context of solid tumor metastasis. #CancerResearch #EZH2 #Metastasis #SolidTumors #Collaboration #ScientificReview

Kickstarting 2025 with insights into #antigen-presenting cell (APC) #reprogramming! We are excited to share our latest review: “Transcription factor-mediated reprogramming to antigen-presenting cells.” In this work, Lund University PhD student Ervin Ascic dives into cutting-edge strategies for generating APCs, bringing us closer to clinical applications in cancer #immunotherapy and beyond. First, we detail #transcription factor (TF) networks instructing the fate of #dendritic cells and #macrophages, which are crucial for mounting an immune response against cancer or infections. Then, we emphasize the promise behind engineering APC cell fates, exploring different approaches to generate these immune subsets, including enrichment from peripheral blood, differentiation from multipotent or pluripotent progenitors, and TF-mediated cellular reprogramming. Lastly, we review the potential of harnessing TF combinations to generate APCs from unrelated cells, namely cancer cells. Specifically, we summarize the evidence showing that direct reprogramming of cancer cells to dendritic cells elicits strong antitumor immunity in vivo. This work showcases the potential of transcription factors in reprogramming immune cells and reshaping immune responses. We’re excited about the opportunities it opens for future #cancer immunotherapies. Read the full paper here: https://lnkd.in/dMj3EMQM

Partnering to Advance Precision Medicine This #KNOWvember, Lung Cancer Canada is proud to collaborate with the Cancer Collaborative, Canadian Breast Cancer Network, Colorectal Cancer Canada, Genome Canada, and Dr. Shaqil Kassam to highlight the transformative power of Precision Medicine. But how does precision medicine work? Genomic Testing: It starts with analyzing a patient’s tumor to uncover specific mutations or biomarkers driving the cancer. Targeted Treatment: Therapies are then matched to these findings, offering tailored care that’s more effective and less invasive. Ongoing Monitoring: Patient response and data guide adjustments, ensuring treatments stay personalized and impactful. By using these tools, precision medicine is revolutionizing cancer care, offering patients more hope, fewer side effects, and better outcomes. Let’s work together to make this innovation accessible to all. Learn more: knowyourgenome.co

Today, I was researching cancer and potential therapies that could be developed and found an interesting review article written by Jovanka Gencel-Augusto, Ph.D., Trever Bivona and Wei Wu. It focuses on research about long non-coding RNAs in lung cancer.🧫   Before reading about the findings, it is crucial to define what lncRNAs are, as mentioned in the article they are "non-protein coding molecules longer than 200 nucleotides. They play essential roles in normal cell function and development, and can contribute to diseases such as cancer when dysregulated."   Key facts from the review include that lncRNAs have highly context-specific functions, making detailed in vivo studies crucial to understanding their roles in physiological processes. They are very stable molecules present in the systemic circulation. And their resistance to degradation by nucleases for example, is attributed to factors such as their secondary structures, transport within exosomes, and stabilizing post-translational modifications. In therapeutic approaches, the way in which lncRNAs operate include inhibiting oncogenic lncRNAs or restoring the function of tumor-suppressive lncRNAs.   Additionally, future research could be developed on how lncRNAs influence immunotherapy responses because this area remains largely unexplored. From my perspective, I would use aptamers to target peptides encoded by lncRNAs and measure the differences on the inhibition of important genes associated with tumor growth from various malignancies. Moreover, it is also possible to make a comprehensive study of their role in signaling pathways and the interactome between coding and non-coding molecules, these findings could significantly enhance our understanding of this topic, benefiting the scientific community. I would highly recommend reading the article if you are interested in this field: https://lnkd.in/ewKPQTWb #lncRNAs #cancer #therapy #cancertherapy #lungcancer #pathways #molecules #regulation #cells

Dr. Marilyn Li, our Director of Cancer Genomic Diagnostics, has been invited to speak at the Future Health Summit at Abu Dhabi Global Healthcare Week on May 14. Dr. Li specializes in the genomic analysis of pediatric tumors using state-of-the-art technology, such as next-generation sequencing and other genomic tools. She will share expert insight on leveraging these advanced and high throughput technologies in cancer research and clinical diagnosis to facilitate precision cancer care. Dr. Li and her group have studied thousands of cancers using multi-omics approaches which have uncovered multidimensional alterations in cancer that are essential for cancer diagnosis, risk stratification, and therapeutic selection. Learn more about Dr. Li's research: http://ms.spr.ly/6046YDpde.

On January 14th during the Open Science Bar on the role of innervation in tumor progression, Dr. Mara Mazzoni and Dr. Tiziana Di Marco presented an overview about the role of peripheral nerves in solid tumors. Dr. Laura Gatti and Dr. Ignazio Vetrano of the Istituto Neurologico Besta acted as discussants. Dr. Mazzoni and Dr. Di Marco focused on the role of innervation in thyroid cancer (for which its function remains to be established) presenting an ongoing project (Figure below) and a possible future project to develop. The aim of the presented studies is to explore the contribution of innervation in thyroid cancer progression. In particular they aimed to evaluate: i) the presence of a neuronal gene signature in thyroid cancer cell lines and in human thyroid tumors; ii) the composition of thyroid cancer cell lines secretome and the capabilities of the thyroid cancer cells secreted factors to induce neuronal differentiation; iii) the crosstalk between thyroid cancer and neuronal cells, in interaction with other tumor microenvironment components. This will provide new knowledge about innervation as a mechanism contributing to tumor progression, helping to unveil new potential druggable targets. #IstitutoTumoriMilano #OSB #OpenScienceBar #ComponenteNervosaPeriferica #TumoriSolidi #PatologiaNeoplasticaTiroidea #TumoreTiroideo #IstitutoNeurologicoBesta

Investigating how platelet-derived extracellular vesicles drive melanoma progression: in their latest work, Zeynep T., Pia Siljander at University of Helsinki and collaborators compared the effects of platelet-derived extracellular vesicles generated through different activation pathways on key cancer hallmark functions. Using 3D spheroids of two melanoma cell types with varying metastatic potential, they conducted multiple functional assays, including proliferation, invasion, tube formation, and cancer EV analysis, alongside RNA sequencing to uncover the mechanisms and signaling pathways driving melanoma progression and metastasis https://lnkd.in/emXZta9Z They proposed that elucidating the molecular interactions between cancer cells and platelets could pave the way for developing antiplatelet strategies more effectively integrated with cancer therapies. An article co-authored by Umar Butt, Alessandra Valeria de Sousa Faria, Johannes Oesterreicher, Wolfgang Holnthoner, Laitinen Saara and Mari Palviainen #extracellularvesicles #exosomes #platelets #melanoma #Vesiculab