Cristina Girao_ Biochemist/MSc Cell Biology/PhD Immunology’s Post

Tumor Intrinsic Subtypes and Gene Expression Signatures in Early-Stage ERBB2/HER2-Positive Breast Cancer A Pooled Analysis of CALGB 40601, NeoALTTO, and NSABP B-41 Trials Question  What is the quantitative association between pathologic complete response (pCR) and event-free survival (EFS) by intrinsic subtype and other gene expression signatures in patients with ERBB2/HER2-positive early breast cancer (EBC) treated in the neoadjuvant setting? Findings  In this retrospective pooled analysis of 3 randomized clinical trials including 1289 patients with ERBB2/HER2-positive EBC, the association between pCR and EFS differed by tumor intrinsic subtype, and the benefit of dual ERBB2/HER2-blockade was limited to ERBB2-enriched tumors. Immune-activated signatures were associated with higher pCR rates and better EFS, whereas luminal signatures were associated with lower pCR rates. Meaning  Intrinsic subtype and immune gene expression biomarkers may help guide personalized treatment in patients with ERBB2/HER2-postive EBC.

MAPK (Mitogen-Activated Protein Kinase) pathways play crucial roles in cell proliferation, differentiation, and survival. In bladder cancer, alterations in MAPK signaling are common and contribute to tumor development and progression. Aberrant activation of MAPK pathways, such as the ERK (Extracellular Signal-Regulated Kinase) pathway, is frequently observed in bladder cancer, leading to uncontrolled cell growth and survival. Targeting these pathways could be a promising approach for bladder cancer treatment. Predicting MAPK pathway activity in bladder cancer involves analyzing various factors like gene expression, mutations, and pathway activation status. Machine learning models can be trained on datasets containing these features to predict MAPK pathway activity in bladder cancer patients. By integrating genomic, transcriptomic, and clinical data, these models can provide insights into patient prognosis, treatment response, and potential therapeutic targets. The following study accurately predicts bladder cancer with survival!! #bioinformatics #R #Machinelearning #Computationalbiology https://lnkd.in/gf-4QneZ

Triple-negative breast cancer represents 15–20% of breast cancer cases and lacks targeted treatments. It is a biologically aggressive tumor characterized by moderate/high grade and highly proliferative cancer cells, which, together with limited treatment options, leads to the poorest prognosis among breast cancer subtypes. BRCA mutations, especially BRCA1, are strongly associated with TNBC risk. As per DelveInsight Business Research LLP’s estimates, out of all gene mutation specific TNBC cases in the United States in 2023, approximately 5,000 cases were BRAC gene mutation cases. Latest results from the PARTNER Trial (NCT03150576) at AACR 2024 assessed LYNPARZA (olaparib) with carboplatin and paclitaxel in neoadjuvant therapy for BRCA Wild-Type TNBC but didn't show improved outcomes compared to chemotherapy alone. For detailed findings, visit: https://lnkd.in/gYtNd8ku #breastcancer #triplenegativebreastcancer #AACR2024 #cancertreatment #neoadjuvant #BRAC #BRACgenemutations #genemutations #Olaparib

“The researchers examined changes in these cells that enabled them to adapt and survive in the presence of an inhibitor. Unexpectedly, global RNA gene analysis revealed that in ER-positive and triple-negative breast cancer cells, resistance to FOXM1 inhibition was accompanied by elevated levels of ferroptosis-suppressing genes. This suggested that acquired resistance to FOXM1 inhibitors could be reversed with inducers of ferroptosis, a type of iron-dependent programmed cell death. Cancer cells are highly dependent on iron for their metabolic activity.” #breastcancer #cancerresearch #drugresistance #ferritin #ERpositivebreastcancer #ERnegativebreastcancer #tumormicroenvironment #FOXM1

Scientists from Northwestern University and University of San Francisco recently published an article in Nature about a gene mutation which showed how a cancerous mutation that fuses a pair of genes, CARD11 and PIK3R3, can enhance the effectiveness of T-cell therapies against cancer in mice. The mutation seems to have strong anti-cancer effects when added to T cells in CAR-T and TCR therapies boosting their ability to kill tumor cells which could be a game-changer for patients with hard-to-treat cancers. Given the recent developments related to the safety of available CAR-T therapies, scientists will need to be cautious to balance improving the efficacy of therapies to expand their use while maintaining, if not improving, their overall safety.  When do you think this approach could be translated to clinical trials? #cellandgenetherapy #celltherapy

This review is about PANoptosis, which merges apoptosis, pyroptosis, and necroptosis, and its implications in cancer. It covers the molecular pathways, emphasizing shared components like caspases and the PANoptosome complex. PANoptosis's role in various cancers, its impact on tumorigenesis, and patient survival rates are discussed, along with its relationship with the tumor microenvironment (TME) and immune cells. The review also highlights a novel approach of cancer therapy by targeting PANoptosis and outlines strategies like targeting key signaling molecules and exploring novel treatments. https://lnkd.in/gmziQu82

#sciencenews 🔬 Exciting Breakthrough in Breast Cancer Research! A Stanford University School of Medicine study uncovered compelling evidence that inherited gene sequences may influence the type and severity of breast cancer decades later. This challenges the traditional belief that cancers arise as a result of random mutations during our lifetimes. Instead, it suggests an active role of inherited gene sequences in determining the immune system's recognition and elimination of potential cancer-causing mutations. These findings have significant implications for predicting cancer recurrence and refining risk stratification within breast cancer subtypes. Read the full article here: https://lnkd.in/gVP3CeQZ #Breastcancerresearch #cancerimmunotherapy #PrecisionMedicine #researchbreakthrough #medicalresearch #biotech #bioscience #scienceofreading

Like pieces in a puzzle, more evidence is accumulating for the "moonlighting" of oncoproteins such as Myc. As we map these proteins to more and more oncopathways, their diverse roles reveal that tumor heterogeneity reflects oncoprotein "moonlighting" and therefore, the diverse interaction networks that drive cancer development and growth. The transcription factor MYC plays a significant role in cancer progression by driving various hallmarks of cancer development. While MYC is known to promote oncogenic transcription by binding to active promoters, it has also been observed to invade distal enhancers, albeit with previously assumed low gene-regulatory potential. However, new findings suggest that MYC directly regulates enhancer activity to promote cancer type-specific gene programs that are predictive of poor patient prognosis. This regulation involves MYC inducing transcription of enhancer RNA through the recruitment of RNA polymerase II (RNAPII), rather than regulating RNAPII pause-release, which is typical at promoters. This induction process is facilitated by MYC-induced H3K9 demethylation and acetylation by GCN5, leading to enhancer-specific BRD4 recruitment through its bromodomains, ultimately facilitating RNAPII recruitment. The study proposes that MYC drives prognostic cancer type-specific gene programs through the induction of an enhancer-specific epigenetic switch, which could be targeted therapeutically by BET and GCN5 inhibitors. These findings shed light on the complex regulatory mechanisms involving MYC in cancer progression and suggest potential therapeutic targets for intervention.

📃Scientific paper: CircRNAs in colorectal cancer: potential biomarkers and therapeutic targets Abstract: Globally, colorectal cancer (CRC) is the third most prevalent cancer and the second leading cause of cancer-related deaths. Circular RNAs (circRNAs) are single-stranded RNA with covalently closed-loop structures and are highly stable, conserved, and abundantly expressed in various organs and tissues. Recent research found abnormal circRNA expression in CRC patients’ blood/serum, cells, CRC tissues, and exosomes. Furthermore, mounting data demonstrated that circRNAs are crucial to the development of CRC. CircRNAs have been shown to exert biological functions by acting as microRNA sponges, RNA-binding protein sponges, regulators of gene splicing and transcription, and protein/peptide translators. These characteristics make circRNAs potential markers for CRC diagnosis and prognosis, potential therapeutic targets, and circRNA-based therapies. However, further studies are still necessary to improve the understanding of the roles and biological mechanisms of circRNAs in the development of CRC. In this review, up-to-date research on the role of circRNAs in CRC was examined, focusing on their potential application in CRC diagnosis and targeted therapy, which would advance the knowledge of the functions of circRNAs in the development and progression of CRC. Continued on ES/IODE ➡️ https://etcse.fr/qH ------- 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.

CAR-T (Chimeric Antigen Receptor T-cell) therapy, a groundbreaking approach to cancer treatment, has its roots in the late 1980s. CAR-T therapy represents a remarkable convergence of immunology and genetic engineering. This innovative therapy involves reprogramming a patient's own T-cells to target and destroy cancer cells. The process starts by extracting a patient's T-cells, genetically modifying them to express chimeric antigen receptors (CARs) specific to cancer antigens, and then infusing them back into the patient's body. The CAR-T cells effectively seek out and attack cancer cells. CAR-T therapy has witnessed significant advancements, particularly in recent years. It has gained FDA approval for treating various blood cancers, including certain types of leukaemia and lymphoma, and has shown remarkable success in clinical trials. CAR-T therapy has offered hope to patients who had exhausted other treatment options, marking a paradigm shift in cancer care. The discovery of CAR-T therapy is credited to Dr. Zelig Eshhar, an Israeli immunologist, who developed the concept in 1989. The evolution of CAR-T therapy exemplifies how scientific breakthroughs can lead to life-saving innovations and change the landscape of cancer treatment. #BioAngelsBiotechChronicles #BioAngels #HealthcareInnovations #HealthcareSolutions