Mohammad Vaziri’s Post

The role of CRAF in cancer progression: from molecular mechanisms to precision therapies. CRAF activation is unique from BRAF activation, it requires input from additional non-MAPK signalling pathways (such as SRC and PAK-family kinases) for optimal kinase activity. CRAF has several important roles in tumourigenesis and therapeutic resistance in cancer. RAF1 alterations are being increasingly identified in clinical practice, but currently, there is no standard therapeutic approach for tumours with RAF1 alterations. In this review authors have presented main known regulatory mechanisms and gene alterations that contribute to CRAF activity, highlighting the different oncogenic roles of CRAF, and categorize RAF1 (CRAF) mutations according to the effect on kinase activity. This work has led to new treatments that improve survival outcomes for patients. There is a high possibility of building on decades of preclinical research on CRAF and incorporate new classes of therapeutics to achieve similar outcomes for patients with RAF1-altered cancers. #RAF1 #drugresistance #drugdiscovery #GTPases #RAS #kinases #ERK #mek #MAPK #cancerresearch #cancertreatment #drugdiscovery #inhibitors #therapeutictarget

📃Scientific paper: Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer Abstract: SIMPLE SUMMARY: In recent years, the incidence of papillary thyroid cancer (PTC) has increased in many countries worldwide. MicroRNAs appear to be important regulators of PTC, but a better understanding of their role is needed to develop novel diagnostic tools and identify potential vulnerabilities. In this study, we aimed to gain insight into the microRNA profile of PTC tissue. Consequently, crucial pathways in PTC were highlighted. A panel of four microRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) was proposed as a PTC diagnostic biomarker. Our analysis indicated that microRNAs are a potential diagnostic tool for PTC patients. ABSTRACT: The incidence of papillary thyroid cancer (PTC) has increased in recent years. To improve the diagnostic management of PTC, we propose the use of microRNAs (miRNAs) as a biomarker. Our aim in this study was to evaluate the miRNA expression pattern in PTC using NanoString technology. We identified ten miRNAs deregulated in PTC compared with reference tissue: miR-146b-5p, miR-221-3p, miR-221-5p, miR-34-5p, miR-551b-3p, miR-152-3p, miR-15a-5p, miR-31-5p, and miR-7-5p (FDR < 0.05; |fold change (FC)| ≥ 1.5). The gene ontology (GO) analysis of differentially expressed miRNA (DEM) target genes identified the predominant involvement of epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor resistance, and pathways in cancer in PTC. The highest area under the receiver operating characteristic (ROC) curve (AUC) for ... Continued on ES/IODE ➡️ https://etcse.fr/ljgy ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Happy Thursday all! Check out this Nature Reviews Cancer article by Riaud et al., about the role of CRAF in cancer progression. Abstract: The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer. Although BRAF is the most studied RAF protein, partially owing to its high mutation incidence in melanoma, the role of CRAF in tumourigenesis and drug resistance is becoming increasingly clinically relevant. Here, we summarize the main known regulatory mechanisms and gene alterations that contribute to CRAF activity, highlighting the different oncogenic roles of CRAF, and categorize RAF1 (CRAF) mutations according to the effect on kinase activity. Additionally, we emphasize the effect that CRAF alterations may have on drug resistance and how precision therapies could effectively target CRAF-dependent tumours. Here, we discuss preclinical and clinical findings that may lead to improved treatments for all types of oncogenic RAF1 alterations in cancer. #drugdiscovery #cancerresearch #precisiononcology #immunotherapy #immunooncology #raf #scientificresearch

In collaboration with Gerry Melino and our partners at University of Rome Tor Vergata, our newest publication has been released in Discover Oncology. Hepatocellular carcinoma (HCC) is a primary liver cancer that often develops resistance to chemotherapy, a phenomenon known as chemoresistance. Powered by the Indivumed Therapeutics Omics Hub, “Genomic and transcriptomic profiling of hepatocellular carcinoma reveals a rare molecular subtype” demonstrates that multi-omics approaches can enable a better understanding of complex cellular and molecular changes, offering a more complete picture of the cancer disease. This could potentially lead to the development of new strategies to predict, prevent, or overcome chemoresistance, improving the effectiveness of HCC treatment. View the full publication: https://lnkd.in/efSMHMge

Exploring the Therapeutic Potential of Snake Venom in Cancer Treatment 🐍 👉 For over half a century, researchers have been fascinated by the potential of cytotoxic agents in cancer therapy. Interestingly, some of the most promising candidates come from nature's deadliest creatures—snakes. Venomous animals, especially snakes, possess potent toxins that have shown remarkable specificity in targeting both healthy and tumoral cells. Among these, enzymes such as metalloproteases, L-amino acid oxidases, disintegrins, and phospholipases A2 have demonstrated significant antitumor activity, inducing apoptosis, inhibiting angiogenesis, and generating free radicals. Clinical research has shown measurable responses in advanced cancer treatment phases, suggesting that snake venom could one day be harnessed to develop powerful new cancer therapies. While the journey from venom to viable drug is long and complex, ongoing research continues to uncover the unique ways these venom components interact with cancer cells, offering hope for more targeted and effective treatments. Could venom be the future of oncology? Let's keep an eye on the fascinating developments in this field! #CancerResearch #Biotechnology #SnakeVenom #Oncology #MedicalInnovation #Biotech #Pharmacology #ResearchAndDevelopment #DrugDiscovery Source : https://lnkd.in/gm6WwAFg

#breastcancer #cancerresearch #oncology #cancertreatment https://lnkd.in/gymyGDMG Abstract Amplification and/or overexpression of ERBB2, the gene encoding HER2, can be found in 15–20% of invasive breast cancers and is associated with an aggressive phenotype and poor clinical outcomes. Relentless research efforts in #molecular #biology and drug development have led to the implementation of several HER2-targeted therapies, including monoclonal antibodies, tyrosine-kinase inhibitors and antibody–drug conjugates, constituting one of the best examples of bench-to-bedside translation in oncology. Each individual drug class has improved patient outcomes and, importantly, the combinatorial and sequential use of different HER2-targeted therapies has increased cure rates in the early stage disease setting and substantially prolonged survival for patients with advanced-stage disease. In this Review, we describe key steps in the development of the modern paradigm for the treatment of HER2-positive advanced-stage breast cancer, including selecting and sequencing new-generation HER2-targeted therapies, and summarize efficacy and safety outcomes from pivotal studies. We then outline the factors that are currently known to be related to resistance to HER2-targeted therapies, such as HER2 intratumoural heterogeneity, activation of alternative signalling pathways and immune escape mechanisms, as well as potential strategies that might be used in the future to overcome this resistance and further improve patient outcomes.

#cancerresearch #oncology #cancertreatment #breastcancer https://lnkd.in/gymyGDMG Abstract Amplification and/or overexpression of ERBB2, the gene encoding HER2, can be found in 15–20% of invasive breast cancers and is associated with an aggressive phenotype and poor clinical outcomes. Relentless research efforts in #molecular #biology and drug development have led to the implementation of several HER2-targeted therapies, including monoclonal #antibodies, tyrosine-kinase inhibitors and antibody–drug conjugates, constituting one of the best examples of bench-to-bedside translation in oncology. Each individual drug class has improved patient outcomes and, importantly, the combinatorial and sequential use of different HER2-targeted therapies has increased cure rates in the early stage disease setting and substantially prolonged survival for patients with advanced-stage disease. In this Review, we describe key steps in the development of the modern paradigm for the treatment of HER2-positive advanced-stage breast cancer, including selecting and sequencing new-generation HER2-targeted therapies, and summarize efficacy and safety outcomes from pivotal studies. We then outline the factors that are currently known to be related to resistance to HER2-targeted therapies, such as HER2 intratumoural heterogeneity, activation of alternative signalling pathways and immune escape mechanisms, as well as potential strategies that might be used in the future to overcome this resistance and further improve patient outcomes.

𝐂𝐮𝐫𝐫𝐞𝐧𝐭 𝐬𝐜𝐞𝐧𝐚𝐫𝐢𝐨 𝐨𝐟 𝐩𝐞𝐫𝐬𝐨𝐧𝐚𝐥𝐢𝐳𝐞𝐝 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭 💊 𝐢𝐧 𝐜𝐚𝐧𝐜𝐞𝐫 The emergence of 𝐛𝐢𝐨𝐦𝐚𝐫𝐤𝐞𝐫 𝐭𝐞𝐬𝐭𝐢𝐧𝐠 has led to the 𝐠𝐞𝐧𝐨𝐦𝐞-𝐰𝐢𝐝𝐞 𝐬𝐜𝐫𝐞𝐞𝐧𝐢𝐧𝐠 𝐨𝐟 𝐜𝐚𝐧𝐜𝐞𝐫. This can identify the causative genes’ mutation, amplification and fusions in various cancers. Based on the underlying genetic mechanism, personalized therapy including 𝐬𝐦𝐚𝐥𝐥 𝐦𝐨𝐥𝐞𝐜𝐮𝐥𝐞 𝐢𝐧𝐡𝐢𝐛𝐢𝐭𝐨𝐫𝐬, 𝐠𝐞𝐧𝐞 𝐭𝐡𝐞𝐫𝐚𝐩𝐲, 𝐢𝐦𝐦𝐮𝐧𝐨𝐭𝐡𝐞𝐫𝐚𝐩𝐲 𝐬𝐮𝐜𝐡 𝐚𝐬 𝐛𝐢𝐨𝐬𝐢𝐦𝐢𝐥𝐚𝐫𝐬, 𝐂𝐀𝐑𝐬, 𝐜𝐡𝐞𝐜𝐤𝐩𝐨𝐢𝐧𝐭 𝐢𝐧𝐡𝐢𝐛𝐢𝐭𝐨𝐫𝐬, 𝐯𝐚𝐜𝐜𝐢𝐧𝐞𝐬 𝐚𝐧𝐝 𝐜𝐲𝐭𝐨𝐤𝐢𝐧𝐞 𝐭𝐡𝐞𝐫𝐚𝐩𝐲 can be administered to the patients. Personalized therapy offers lesser side effects as it targets the contributing factor, however, is unable to reach the masses due to ☛ ✷ 𝑯𝒊𝒈𝒉 𝒄𝒐𝒔𝒕 𝒐𝒇 𝒅𝒊𝒂𝒈𝒏𝒐𝒔𝒊𝒔 𝒂𝒏𝒅 𝒕𝒓𝒆𝒂𝒕𝒎𝒆𝒏𝒕 ✷ 𝑻𝒊𝒎𝒆 𝒕𝒂𝒌𝒆𝒏 𝒇𝒐𝒓 𝒅𝒊𝒂𝒈𝒏𝒐𝒔𝒊𝒔 ✷ 𝑵𝒐𝒕 𝒂𝒗𝒂𝒊𝒍𝒂𝒃𝒍𝒆 𝒇𝒐𝒓 𝒂𝒍𝒍 𝒄𝒂𝒏𝒄𝒆𝒓𝒔, 𝒂𝒔 𝒔𝒐𝒎𝒆 𝒕𝒂𝒓𝒈𝒆𝒕𝒔 𝒂𝒓𝒆 𝒖𝒏𝒅𝒓𝒖𝒈𝒈𝒂𝒃𝒍𝒆 ✷ 𝑺𝒐𝒎𝒆 𝒕𝒉𝒆𝒓𝒂𝒑𝒊𝒆𝒔 𝒂𝒓𝒆 𝒊𝒏 𝒕𝒓𝒊𝒂𝒍𝒔 ✷ 𝑾𝒐𝒓𝒌𝒔 𝒃𝒆𝒔𝒕 𝒊𝒏 𝒄𝒐𝒎𝒃𝒊𝒏𝒂𝒕𝒊𝒐𝒏, 𝒐𝒘𝒊𝒏𝒈 𝒕𝒐 𝒕𝒉𝒆𝒓𝒂𝒑𝒚 𝒓𝒆𝒔𝒊𝒔𝒕𝒂𝒏𝒄𝒆 Points to improve ☛ ◆ 𝑴𝒐𝒍𝒆𝒄𝒖𝒍𝒂𝒓 𝒕𝒖𝒎𝒐𝒓 𝒃𝒐𝒂𝒓𝒅: Adopting multi-omics approach to understand the novel and lesser-known players ◆ 𝑷𝒂𝒕𝒊𝒆𝒏𝒕-𝒅𝒆𝒓𝒊𝒗𝒆𝒅 𝒐𝒓𝒈𝒂𝒏𝒐𝒊𝒅𝒔 𝒂𝒏𝒅 𝒙𝒆𝒏𝒐𝒈𝒓𝒂𝒇𝒕𝒔: cancer evolution, clonal selection and sensitivity upon drug exposure ◆ 𝑳𝒊𝒒𝒖𝒊𝒅 𝒃𝒊𝒐𝒑𝒔𝒚: Understanding tumor heterogeneity better relative to single biopsy The following news highlights the recent FDA approved targeted therapies in cancer in 2024 ☟ #cancer #targetedtherapy

Source: Journal of pharmaceutical and biomedical analysis A study found distinct differences in the plasma molecular profiles of early-onset and late-onset colorectal cancer patients. Using metabolomics and lipidomics analyses, the study identified specific metabolites and lipids that were altered in the colorectal cancer group. The analysis also revealed that early-onset colorectal cancer patients had unique metabolomic and lipidomic profiles compared to late-onset patients. Gene expression data further supported these distinctions. The findings provide insights into the development mechanisms of early-onset colorectal cancer and potential plasma biomarkers for diagnosis.

The SOLTI-1402 CORALEEN phase II study revealed that neoadjuvant treatment with #letrozole and #ribociclib in high-risk early stage Luminal B breast cancer patients resulted in molecular downstaging, as evidenced by a substantial degree of intrinsic subtype conversion to Luminal A and a decrease in Ki67 immunohistochemistry expression. Both therapies resulted in a decrease in Ki67 and an increase in cell cycle arrest (CCCA); however, the mechanisms through which CCCA was achieved differed between the ribociclib and letrozole arm and the chemotherapy arm. Gene expression analysis indicated that the combination of ribociclib and letrozole did not demonstrate enrichment in cell populations with tumor-initiating properties, unlike traditional cytotoxic chemotherapy and letrozole monotherapy. The study found that changes in TIL (Tumor Infiltrating Lymphocytes) quantification may not be a reliable marker of response or as a comprehensive indicator of immune microenvironment change in the Luminal B population. Gene expression signatures associated with antigen-presenting cells showed increased expression in CCCA tumors post-chemotherapy, while the same modules displayed decreased expression after ribociclib and letrozole treatment. #cancerresearch #drugdiscovery #clinicalresearch https://lnkd.in/eH38xTsT