Gencurix, Inc.’s Post

In newly diagnosed advanced nonsquamous non–small cell lung cancer (NSCLC), undergenotyping and incomplete genotyping for genomic biomarkers that are guideline-recommended poses a significant challenge to informative and timely clinical decision-making.¹ In one of the largest prospective, multicentre cell-free DNA (cfDNA) studies in previously untreated metastatic non-small cell lung cancer (mNSCLC), it was demonstrated that a validated, highly sensitive and highly specific, clinically utilized comprehensive cell-free DNA (cfDNA) test (Guardant360®) detects guideline-recommended biomarker-positive patients at a rate similar to standard of care (SOC) tissue genomic testing, with high concordance and significantly faster return of test results (in 9 days vs. 15 days) leading to complete genotyping of the guideline-recommended biomarkers in more patients (95% vs. 31%).¹ These findings from the NILE (Non-invasive versus Invasive Lung Evaluation) study demonstrate that Guardant360 can be a clinically viable alternative to tissue-based genotyping for first-line therapy selection in patients with newly diagnosed advanced NSCLC.¹ This is one of many factors that makes our liquid biopsy solid. Visit us at https://lnkd.in/dVEkKyRC to find out more about our comprehensive genomic profiling tests that can help guide treatment decisions for patients with cancer. These tests are for prescription use only. Speak to your doctor today about comprehensive genomic profiling. Reference: 1. Leighl NB, Page RD, Raymond VM, et al. Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non-small Cell Lung Cancer. Clin Cancer Res. 2019;25(15):4691-4700. doi:10.1158/1078-0432.CCR-19-0624 #guardanthealth #guardanthealthamea #liquidbiopsy #liquidissolid #lungcancer #NSCLC #comprehensivegenomicprofiling #nextgenerationsequencing #NGS #cancerpatients #medicaloncologists

Patients with resectable stage IB-IIIA, IIIB (T3, N2) NSCLC are usually only offered testing for ALK and EGFR mutations to determine their eligibility for neoadjuvant therapy. However, data suggests these early-stage patients may harbor additional actionable mutations. In fact, the International Association for the Study of Lung Cancer now “highly encourages” biomarker testing for oncogenic drivers other than EGFR and ALK alterations in patients with early-stage disease. We're initiating a study to identify additional actionable mutations in this patient population, offering a unique opportunity to gather data in a timely and cost-effective manner. The information may then be used to design future definitive clinical trials that aim to expand the list of actionable genomic alterations for this patient population, which could make targeted treatment options available to a larger group of patients. Learn more and get involved here: https://hubs.ly/Q02YhFF30 #ALK #EGFR #neoadjuvanttherapy #lungcancer #NSCLC #cancer #clinicalstudy #clinicaltrial

We're happy to share our 2024 Breast Cancer research publication list! This year, our laboratory (Molecular Signaling & Drug Discovery Laboratory) has continued to make significant strides in understanding and combating this disease. Mainly, our research focuses on developing novel therapies targeting Molecular Signaling in breast cancer. We are also dedicated to understanding the underlying molecular mechanisms of breast cancer development and progression. Key findings from our publications this year include identification of molecular signaling inhibitor(s) and signaling pathway modulation by Natural/Synthetic/Semi-synthetic molecules or MicroRNAs View our complete 2024 breast cancer research publication list here: 1.     Discovery of anticancer compound possessing potential to bind γ-secretase catalytic subunit and inhibit notch promoter activity PMID: 38345058 DOI: 10.1080/07391102.2024.2315323 2.     Kurarinone targets JAK2‐STAT3 signaling in colon cancer‐stem‐like cells PMID: 38390770 DOI: 10.1002/cbf.3959 3.     Withaferin A alters the expression of microRNAs 146a-5p and 34a-5p and associated hub genes in MDA-MB-231 cells PMID: 38525814 DOI: 10.1515/bmc-2022-0045 4.     Role of ONECUT family transcription factors in cancer and other diseases PMID: 38593917 DOI: 10.1016/j.yexcr.2024.114035 5.     Recent update on IGF-1/IGF-1R signaling axis as a promising therapeutic target for triple-negative breast cancer PMID: 39357179 DOI: 10.1016/j.prp.2024.155620 6.     Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics DOI: 10.1007/s11095-024-03811-1 We are grateful for the financial supports from: Department of Science & Technology, New Delhi, India Indian Council of Medical Research, New Delhi, India University rants Commissions, New Delhi, India Central University of Punjab, Punjab, India #Indian Council of Medical Research (ICMR) #DSTIndia #indianuniversity #ugc

Do you want to develop a best-in-class drug? Use 𝗚𝗲𝗻𝗶𝗮𝗹𝗶𝘀™ 𝗸𝗿𝗮𝘀𝗜𝗗 - our first-in-class RNA biomarker that classifies response to and benefit from KRAS inhibitors. The evidence? Genialis krasID classifier can predict response: ✅ with >𝟵𝟰% 𝗮𝗰𝗰𝘂𝗿𝗮𝗰𝘆 across multiple different KRASi in preclinical models and ✅ with >𝟴𝟬% 𝗮𝗰𝗰𝘂𝗿𝗮𝗰𝘆 in real world patients. Read more: https://lnkd.in/dNSFdeAm #kras Genialis #biomarker #precisiononcology #machinelearning #cancer #AACR24 AACR Journals

"Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors without resorting to advanced genomic or immunologic assays is an important clinical need," Memorial Sloan Kettering Cancer Center and Mount Sinai Health System researchers describe in a new Springer Nature's Nature publication. Aiming to address this challenge, investigators including CRI Scientific Advisory Council Associate Director Dr. Nina Bhardwaj, CRI Clinical Innovator Dr. Thomas Marron, CRI Scientific Advisory Council member Dr. Miriam Merad, and former CRI Technology Impact Award recipient Dr. Brian Brown developed SCORPIO, a tool that uses artificial intelligence to predict how well cancer patients will respond to immune checkpoint inhibitors. "Not only does SCORPIO rely on widely available and affordable routine blood tests, but it also consistently outperforms existing Federal Drug Administration-approved biomarkers, such as tumor mutational burden (TMB) and PD-L1 immunostaining, in predicting patient responses to immune checkpoint inhibitors," Mount Sinai Health System describes. "This sets a new benchmark for precision oncology tools." Explore: https://lnkd.in/eQijmv6B #CancerResearch #AI #Immunotherapy

Today I'm rocking my #KnowKRAS wrist band from the KRAS Kickers booth at #aacr24 (thanks Terri Conneran). Because today marks the first day that Genialis has officially entered the fray to help treat and cure KRAS-driven cancers. If your goal is to know KRAS, and to truly understand each patient's biology to ensure they get the right drug (or combination) at the right time, you can't do better than Genialis krasID. This is the first and only biomarker that predicts response and benefit to KRAS inhibitors, designed to work across mutations and disease settings. Check out our poster at AACR today, or download it here at www.genialis.com/krasID

The era of one-size-fits-all cancer therapies has run its course. Today is a new dawn. Introducing 𝗚𝗲𝗻𝗶𝗮𝗹𝗶𝘀™ 𝗸𝗿𝗮𝘀𝗜𝗗: a new AI/ML classifier that accurately predicts KRAS outcomes in lung cancer patients. 💡 Most biomarkers in the KRAS space measure only KRAS mutation status, which • may be necessary to receive the drug • but is insufficient ❌ to predict response or to inform further therapeutic interventions. Genialis krasID works better because it is built differently. By using high-dimensional gene expression data and a ML algorithm ⚙️ comprising numerous biologic signatures, it captures a more complete view of the underlying biology 𝘂𝗻𝗶𝗾𝘂𝗲 𝘁𝗼 𝗲𝗮𝗰𝗵 𝗶𝗻𝗱𝗶𝘃𝗶𝗱𝘂𝗮𝗹 𝗽𝗮𝘁𝗶𝗲𝗻𝘁. Today at #AACR24, we are presenting a poster on the performance of Genialis krasID in predicting clinical benefit in a real-world cohort of patients who received sotorasib, a KRAS inhibitor currently approved for KRAS G12C non-small cell lung cancers. 💊 Today’s initial results demonstrate that the Genialis krasID classifier can predict response: ✅ with >𝟵𝟰% 𝗮𝗰𝗰𝘂𝗿𝗮𝗰𝘆 across multiple different KRASi in preclinical models and ✅ with >𝟴𝟬% 𝗮𝗰𝗰𝘂𝗿𝗮𝗰𝘆 in real world patients. Read more: https://lnkd.in/dNSFdeAm Because the model incorporates biologies that are intrinsic to KRAS function in the tumor and extrinsic to the surrounding tumor milieu, this biomarker is able to perform well for different drugs across KRAS-driven cancers. 🔄 AACR marks the launch of an 𝗲𝗮𝗿𝗹𝘆 𝗮𝗰𝗰𝗲𝘀𝘀 𝗽𝗿𝗼𝗴𝗿𝗮𝗺 for Genialis krasID, where members will gain the opportunity to test drive the biomarker model on their data 🔎 and establish a foundation for implementing the biomarker within their translational workflows. Read more: https://lnkd.in/daMu6VAu Together, we are transforming medicine through data. 🤝

How targeting EP4 receptor can transform #immunotherapy and improve patient outcomes? EP4 antagonists, which inhibit the EP4 receptor, represent a captivating frontier in #immunooncology. A deeper understanding of their potential applications could lead to significant advancements in #cancertreatment. The EP4 receptor is the G protein coupled receptor (GPCR) that, upon binding with its natural Prostaglandin E2 (PGE2), can trigger immune cell modulation, suppressing the immune response and promoting cancer cell survival and proliferation. While COX-2 inhibitors, which aim to inhibit the COX-2 enzyme responsible for PGE2 production, have shown promise in addressing immunosuppression, their development has been hindered by safety concerns. New approaches are needed, and research published in Nature by Jan Böttcher and George Coukos has linked PGE2 released by tumor cells to the inhibition of tumor-infiltrating lymphocytes (TILs) by modulating IL-2 signaling. Additionally, Julian Downward’s research in AACR Journals highlights that KRAS promotes COX-2 expression leading to PGE2 secretion. Yet, the resistance to KRAS targeting therapies is associated with PGE2 revival, risking tumor relapse. These findings underscore the potential risk of triggering PGE2-mediated immunosuppression in patients undergoing TIL-ACT and KRAS therapies. At Domain, we are unlocking the full therapeutic potential of GPCRs to deliver game-changing therapies. By effectively blocking EP4 receptor, our lead clinical candidate, DT-9081, has the potential to be best-in-class in dampening immunosuppressive cells while simultaneously boosting the activity of immunocompetent cells, offering an improved safety profile compared to current treatments. With a strong biomarker plan in place, we believe that DT-9081 holds promise in increasing the efficacy of cancer immunotherapies and extending the range of innovative treatments available to cancer patients. Let’s work together to bring new hope to patients worldwide! 🌍💡 #CancerResearch #drugdevelopment #biotechnology

Paper of the Week: This week's paper by Ricciuti et al. investigates the role of complement activation and neutrophil reprogramming in the tumor microenvironment (TME) of metastatic epithelial ovarian cancer (EOC). The study evaluates serum biomarkers, including complement activation (C3b/c), neutrophil degranulation (MPO), and NET markers, in newly diagnosed EOC patients. While elevated serum levels of gDNA, MPO, and NET markers were independently associated with worse overall survival (OS) in multivariate analyses, C3b/c levels alone were not. However, exploratory analyses revealed that patients with low C3b/c combined with low NET markers had significantly better 2-year OS (87% vs. 46% in others), suggesting a potential interaction between complement and NETs in influencing outcomes. Additionally, increased factor H, a complement inhibitor, in ascites fluid was associated with improved OS, highlighting the complex role of complement regulation in EOC progression. These findings underscore the potential of complement-related biomarkers for prognostic use in EOC, though further validation is needed. Read more here: https://lnkd.in/eKskbr7S 

Most Comprehensive Molecular KRAS Portrait to Date Can Inform Pancreatic Cancer Treatment Response Researchers published two separate articles “Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers,” and “Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer,” published in Science, say they have developed the most comprehensive molecular portrait of the oncogene KRAS and how its activities affect outcomes for pancreatic cancer. The research could help clinicians to select more targeted treatment options for pancreatic cancer patients. Because less than 40% of pancreatic cancers respond to treatment with KRAS inhibitors, if we can establish molecular markers to predict which patients will respond, we can better provide them with specific treatments, which should improve their outcomes. While KRAS is one of the most commonly mutated genes across all cancer types, and is present in more than 90% pancreatic cancers, its mechanisms for promoting cancer growth are still largely unknown. This knowledge gap was the basis of the new findings from the research team. In what they describe as the most detailed analysis of KRAS to date, the investigators showed that the molecular pathway most responsible for the cancer-promoting functions of the oncogene is highly dependent on the ERK protein. ERK regulates which genes are expressed and which proteins are active. The ERK protein has been broadly studied since it is known to be a significant player in the function of KRAS, but its role has remained unclear. Two KRAS inhibitors have been approved for treatment to date and, since it is such a prevalent and promising target, there are a number of KRAS targeting drugs moving through clinical trials. The investigators of the earlier studies showed that the MYC oncogene can cause resistance to KRAS therapies. The papers published in Science established that MYC is a significant component of how both KRAS and ERK support cancer growth and that it is also a driver of therapy resistance to KRAS and ERK targeting therapies. #opportunities #strategy #programming #design #team #research #data #health #development #collaboration #projects #testing #immunotherapy #cancer #technology #biotechnology #healthcare #medicine #oncology #precisionmedicine #liquidbiopsy #rna #dna #venturecapital #startup #immunooncology #tcells #innovation #growth #tech #lifesciences #biopharma #oncodxrx