Exploration of Targeted Anti-tumor Therapy’s Post

Unlocking the secret language of cells: microRNA discoveries have ignited a new era in cancer treatment and hope. The Nobel Assembly at the Karolinska Institutet has today decided to award the 2024 Nobel Prize in Physiology or Medicine to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation. microRNAs in cancer therapeutics: 1) microRNAs are small non-coding RNAs that regulate several genes post-transcriptionally by complementarity pairing. 2) Since their discovery, they have been reported to be involved in a variety of biological functions and pathologies including cancer. 3) In cancer, they can act as a tumor suppressor or oncomiR depending on the cell type. 4) Studies have shown that microRNA-based therapy, either by inhibiting an oncomiR or by inducing a tumor suppressor, is effective in cancer treatment. mRNA in cancer therapeutics: 1) mRNA technology allows the production of diverse vaccines and treatments in a shorter time frame and with reduced expense compared to conventional approaches 2) Approaches are aiming to encode tumour antigens for cancer vaccines, cytokines for immunotherapy, tumour suppressors to inhibit tumour development, chimeric antigen receptors for engineered T cell therapy or genome-editing proteins for gene therapy 3) Given the evidence supporting the effectiveness and safety of clinically approved mRNA vaccines, coupled with growing interest in mRNA-based therapeutics, mRNA technology is poised to become one of the major pillars in cancer drug development. 4) We should anticipate the translation of promising mRNA-based treatments into clinical applications, to ultimately benefit patients in the near future. Learn more Press release: https://bit.ly/4dEie37 Advanced information: https://bit.ly/3Y2fiIZ #medicine #research #healthcare #health #drugdevelopment #pharmaceutical #oncology #cancer #cancerresearch #innovation #technology

The recent study published in Frontiers in Oncology (https://lnkd.in/gkjSBeFu) highlights the role of miR-198 in targeting TOPORS, a protein implicated in the pathogenesis of oral squamous cell carcinoma. This research underscores miR-198's potential as a tumor suppressor across various cancer types. At Speratum Biopharma, Inc. we are advancing this potential by developing NM-198, a therapeutic that leverages miR-198's tumor-suppressing properties. To ensure precise and effective delivery of NM-198, we utilize our proprietary Nano-in™ and NoPass™ platforms. The Nano-in™ platform employs a biocompatible polymer, LGA-PEI, which condenses with nucleic acids to form nanoparticles suitable for in vivo drug delivery. This system has demonstrated a favorable preclinical toxicity profile, indicating its safety and efficacy in delivering therapeutic agents. PR Newswire Complementing this, our NoPass™ technology provides a reprogrammable and flexible platform engineered for robust RNA interference. It enables the non-canonical processing of microRNAs and siRNAs, facilitating the efficient administration of therapeutic agents like NM-198 while minimizing potential off-target effects. Speratum By integrating these platforms, Speratum Biopharma aims to deliver NM-198 with precision, effectively suppressing tumors across various cancer types. This approach not only enhances the therapeutic potential of miR-198 but also ensures the safety and efficacy of our treatments through advanced delivery mechanisms. #precisiononcology, #oncology, #speratumbiopharma

Even 10 Minutes Matter in Cancer Research A recent study conducted by Indivumed Therapeutics highlights a crucial, yet often overlooked, factor in cancer research: the cold ischemia time (CIT), or the time it takes to preserve tumor tissues after surgical removal. This seemingly technical detail—whether tissue samples are snap-frozen within 10 minutes or after a longer delay—can profoundly alter the molecular characteristics of the samples, which in turn impacts the discovery of new cancer drug targets. The findings, published in Cell Death & Disease (link in the comments), reveal that even short delays in preservation can lead to significant shifts in gene expression and protein activity, complicating efforts to accurately identify novel drug targets. The research team at Indivumed conducted a multi-omics analysis on more than 1,800 tumor and matched normal tissue samples from patients with colorectal cancer, liver cancer, and two subtypes of lung cancer. They compared the molecular profiles of samples frozen within 10 minutes after removal to those frozen after a delay of 25 minutes or more. The differences were striking. Samples subjected to longer cold ischemia times exhibited substantial deviations in both gene expression and protein phosphorylation patterns. These changes obscure the true biology of the tumor, leading to potentially misleading conclusions in drug discovery. This research underscores the importance of rapid tissue handling protocols for ensuring the reliability of molecular data, a critical step in precision oncology. As Silvia von der Heyde, Senior Data Scientist at Indivumed Therapeutics, notes, this can result in "wasting time and resources on false leads," or worse, missing critical targets that could yield highly effective treatments. Read BioPharmaTrend.com coverage on website (link in the comments) #cancerresearch #biotech #biopharmatrend

Phenotypic plasticity is a cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Clinical data show that squamous transition occurs in certain lung adenocarcinoma patients who relapse from targeted therapy using EGFR tyrosine-kinase inhibitors (TKIs) or KRAS inhibitor. However, the epigenetic regulatory mechanisms involved in AST remain largely unknown. - TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition - Tet2 knockout in KrasG12D;Lkb1-/- (KL) model suppresses squamous transition through immune microenvironment remodeling - TET2 is recruited to Cxcl5 promoter region via the interaction with STAT3, resulting in Cxcl5 promoter demethylation and gene expression - Therapeutic strategies to control AST process include targeting STAT3 activation, reducing CXCL5 level, or blocking lipid transfer - Study uncovers epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication What are your thoughts on the potential therapeutic strategies identified in this study to inhibit lung cancer transition? #medicalinnovation #cancerresearch #lungcancer #sciencex

🔬🎓 Exciting Announcement from my PhD Research! 🎓🔬 I'm happy to share my recent publication stemming from my doctoral work. Title: "Unveiling the Mechanisms of Extracellular ATP-Mediated Drug Resistance in Human Cancer Cells: Insights from Temporal and Spatial Dynamics" In our study, we delved into the complex landscape of drug resistance mechanisms in cancer, a critical aspect contributing to a significant number of cancer-related deaths. Our investigation spanned diverse temporal and spatial mechanisms, shedding light on how ATP-binding cassette (ABC) transporters, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), glutathione (GSH), senescence, and vacuole-type ATPase (V-ATPase) collectively orchestrate resistance to drug therapies. One of the pivotal findings of our research is the role of extracellular ATP (eATP) in driving drug resistance. We uncovered that eATP not only induces and regulates EMT, CSC formation, and ABC transporters but also consistently upregulates Stanniocalcin-1 (STC1), a gene intricately linked with these processes and tumor growth. Furthermore, our study elucidates a novel pathway through which eATP enhances drug resistance in cancer cells. By mediating eATP internalization via macropinocytosis, intracellular ATP (iATP) levels are elevated, culminating in the induction of EMT and CSC formation, thus fostering drug resistance. This comprehensive investigation represents a significant advancement in our understanding of eATP-induced drug resistance, shedding light on previously unexplored territory. By unraveling these intricate mechanisms, we pave the way for the development of more targeted and effective therapeutic strategies against drug-resistant cancers. I extend my heartfelt gratitude to my advisors, colleagues, and collaborators for their invaluable support and contributions throughout this journey. Together, we're making strides in the fight against cancer. Read the full paper here: https://lnkd.in/eShruD3z and let's continue pushing the boundaries of cancer research together! #PhDResearch #CancerDrugResistance #ExtracellularATP #EMT #CancerStemCells #Innovation

The management of lung cancer (LC) requires the analysis of a diverse spectrum of molecular targets, including kinase activating mutations in EGFR, ERBB2 (HER2), BRAF and MET oncogenes, KRAS G12C substitutions, and ALK, ROS1, RET and NTRK1-3 gene fusions. Administration of immune checkpoint inhibitors (ICIs) is based on the immunohistochemical (IHC) analysis of PD-L1 expression and determination of tumor mutation burden (TMB). Clinical characteristics of the patients, particularly age, gender and smoking history, significantly influence the probability of finding the above targets: for example, LC in young patients is characterized by high frequency of kinase gene rearrangements, while heavy smokers often have KRAS G12C mutations and/or high TMB. Proper selection of first-line therapy influences overall treatment outcomes, therefore, the majority of these tests need to be completed within no more than 10 working days. Activating events in MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option for some laboratories. RNA next-generation sequencing (NGS) is capable of detecting the entire repertoire of druggable gene alterations, therefore it is gradually becoming a dominating technology in LC molecular diagnosis. 🎬 Current status of molecular diagnostics for lung cancer 📝 Authors: Evgeny N. Imyanitov *, Elena V. Preobrazhenskaya, Sergey V. Orlov 📚 This article belongs to the special issue Integrated Approaches for Non-Small-Cell Lung Cancer 👨⚕️Guest Editor: Prof. Dr. Alessandro Morabito and Dr. Edoardo Mercadante, MD, PhD 🏃♂️ Welcome to read, forward, and share the article! https://lnkd.in/gQi54-BK 📄 PDF: https://lnkd.in/gXBYEZy8 #LungCancer #Mutations #Fusions #PredictiveMarkers #Therapy

#cancerresearch #oncology #cancertreatment #biology #medicine #medicalsciences  https://lnkd.in/gyU3QJhP Abstract The emergence of #drug #resistance is the most substantial challenge to the effectiveness of #anticancer #therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant ‘persister’ (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit remarkable plasticity, being capable of transitioning between different cellular states, resulting in distinct DTP phenotypes within a single tumour. However, defining the biological features of DTPs has been challenging, partly due to the complex interplay between clonal dynamics and tissue-specific factors influencing their phenotype. Moreover, the interactions between DTPs and the tumour microenvironment, including their potential to evade immune surveillance, remain to be discovered. Finally, the mechanisms underlying DTP-derived drug resistance and their correlation with clinical outcomes remain poorly understood. This Roadmap aims to provide a comprehensive overview of the field of DTPs, encompassing past achievements and current endeavours in elucidating their biology. We also discuss the prospect of future advancements in technologies in helping to unveil the features of DTPs and propose novel therapeutic strategies that could lead to their eradication.

𝗧𝗮𝗿𝗴𝗲𝘁𝗶𝗻𝗴 𝗺𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝘀𝗺 𝘁𝗼 𝘁𝘂𝗿𝗻 "𝗰𝗼𝗹𝗱" 𝘁𝘂𝗺𝗼𝗿𝘀 𝗶𝗻𝘁𝗼 "𝗵𝗼𝘁" 𝘁𝘂𝗺𝗼𝗿𝘀 𝘁𝗼 𝗲𝗻𝗵𝗮𝗻𝗰𝗲 𝗶𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆 𝗿𝗲𝘀𝗽𝗼𝗻𝘀𝗲 𝗿𝗮𝘁𝗲𝘀? In spite of all the progress that immunotherapy has brought in treating several types of cancers, non-response remains a topic that severly limits the outcomes that patients have achieved. Finging ways to turn so-called "cold" tumors in "hot" ones is thus a field of research that addresses a huge medical need. Both host and microbial metabolism are known to be important in affecting tumor tissue and immune processes in the tumor microenvironment alike. They have also been found to affect the response to immunotherapy. No wonder that the paper that I would like to share today spends a significant proportion on discussing immunometabolism and the role of the microbiome in this setting. https://lnkd.in/euQ9dRqn Full publication: Wu, B., Zhang, B., Li, B. et al. Cold and hot tumors: from molecular mechanisms to targeted therapy. Sig Transduct Target Ther9, 274 (2024). https://lnkd.in/eGDU8MPu. Freely available via a Creative Commons license: https://lnkd.in/d72Y4gs6 #science #metabolism #oncology #pharmacology #precisionmedicine

Last week’s top insights reflect a dynamic shift in the landscape of medical treatment, showcasing advanced therapies that bring hope to patients with previously untreatable conditions. Here are the five most compelling industry insights that you should know about. 1. CAR T-Cell Therapy for Sarcoma: 

Early results from a Phase I trial at Baylor College of Medicine reveal promising outcomes for advanced HER2-specific sarcoma with a 50% clinical benefit rate. Researchers aim to enhance the therapy's potency by optimizing CAR T cell expansion and persistence. Learn more: https://lnkd.in/ejbUwdmW (Inside Precision Medicine)
 2. Revival of Cancer Vaccines:

 Moderna and Merck's large UK trial and BioNTech's promising results in pancreatic cancer mark a turning point for cancer vaccines, leveraging personalized approaches and mRNA technology to target specific tumor mutations. Learn more: https://lnkd.in/enUKfwNR (MIT Technology Review)
 3. Pfizer’s Gene Therapy for Hemophilia B:

 The FDA has approved Pfizer's BEQVEZ, a groundbreaking gene therapy offering a potential lifelong treatment for patients with hemophilia B by enhancing their blood clotting capabilities. Learn more: https://lnkd.in/etqXFcY8 (Genetic Engineering & Biotechnology News) 4. Astellas and Poseida’s Cell Therapy Deal:

 Astellas Pharma's collaboration with Poseida Therapeutics aims to develop "off-the-shelf" cell therapies for solid tumors, enhancing the scalability and accessibility of cancer treatment. Learn more: https://lnkd.in/eyPSyiyB (BioPharma Dive)
 5. mRNA Vaccine for Glioblastoma: 

University of Florida researchers have developed an innovative mRNA cancer vaccine that shows rapid immune activation against glioblastoma in early trials, signaling potential new treatments for one of the most aggressive cancers. Learn more: https://lnkd.in/eucNKYPc (Inside Precision Medicine)
 Follow us for more industry insights each week. #Medicine #Biotech #Pharmacy #Cancer #CART #Insight #Science

#Allogeneic #ChimericAntigenReceptor (CAR) #TcellTherapies, derived from healthy donors, offer a promising approach to #CancerTreatment by providing standardized and cost-effective therapeutic options. However, their #clinicalApplication has been limited due to potential immune rejection and graft-versus-host disease (GVHD). Recent research has identified that the ablation of the FAS gene in allogeneic CD3-negative CAR T cells can enhance their persistence and efficacy in targeting cancer cells, while minimizing the risks of GVHD and immune rejection. 10 Key Takeaways: 1. Allogeneic CAR-T Cells: Utilizing donor-derived CAR T cells can facilitate rapid and standardized cancer therapies. 2. Challenges: Immune rejection and GVHD are significant obstacles in the clinical use of allogeneic CAR T cells. 3. FAS Gene Role: The FAS gene is involved in programmed cell death, influencing the survival of T cells. 4. Gene Ablation Strategy: Removing the FAS gene in CD3-negative CAR T cells enhances their longevity and anti-tumor activity. 5. Reduced GVHD Risk: FAS-deficient CAR T cells demonstrate a lower propensity to cause GVHD. 6. Improved Persistence: These modified cells show increased persistence in the host, leading to sustained therapeutic effects. 7. Enhanced Efficacy: The ablation of FAS results in more effective targeting and elimination of cancer cells. 8. Clinical Implications: This approach holds potential for developing safer and more effective allogeneic CAR T cell therapies. 9. Broader Applications: The findings may extend to other forms of immunotherapy requiring prolonged T cell activity. 10. Future Research: Further studies are needed to validate these results in clinical settings and explore potential side effects. #AllogeneicCART #CancerImmunotherapy #FASGene #GVHD #TCellTherapy #GeneEditing #OncologyResearch #ImmunotherapyAdvancements #CellTherapy #CancerTreatment Source: https://lnkd.in/d8gc7Khy