D3S-001: A KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities

D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Inhibits Nucleotide Cycling and Demonstrates Robust Preclinical and Clinical Activity Background Introduction The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutation is one of the oncogenic drivers in various solid tumors (such as non-small cell lung cancer (NSCLC) an...

Identification of Clonal Hematopoiesis Driver Mutations Through In Silico Saturation Mutagenesis

Introduction In the process of healthy hematopoiesis, a group of hematopoietic stem cells (HSC) contribute to all blood-related lineages. However, as we age, this process often leads to clonal hematopoiesis (CH), meaning the expansion of clones originating from a particular HSC, which then occupies a significant portion of blood cells and platelets...

Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells

In the current field of tumor treatment, precision medicine continues to be a research hotspot and development trend. With the advancement of science and technology, we have begun to more accurately understand the characteristics of tumor cells and their dependencies for survival, in hopes of finding new therapeutic targets. Particularly, strategie...

ror2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma

ror2 regulates cellular plasticity in pancreatic neoplasia and adenocarcinoma

Research Report: The Regulatory Role of ROR2 in Pancreatic Cancer Cell Plasticity Background Introduction Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with most patients lacking the possibility of a cure. This is partly due to the difficulty in early detection. One of the characteristics of PDAC is its extensive tumor cell heterogene...

The N6-Methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma

The N6-Methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma

The Epitranscriptomic Landscape of N6-Methyladenosine Modification in Lung Adenocarcinoma Background Lung cancer is one of the most common cancers globally and a leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung cancer cases, among which lung adenocarcinoma (LUAD) is of particular conc...

ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-targeted Therapy Resistance in Prostate Cancer

ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-targeted Therapy Resistance in Prostate Cancer

ZNF397 Deficiency Triggers TET2-Driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer Academic Background and Research Motivation Existing research evidence suggests that cancer cell lineage plasticity and epigenetic reprogramming enable them to evade lineage-dependent targeted therapy by adopting lineage plasticity. Howev...

CRISPR dependency screens in primary hematopoietic stem cells identify KDM3B as a genotype-specific vulnerability in IDH2- and TET2-mutant cells

CRISPR-Dependent Screening in Primary Hematopoietic Stem Cells Identifies KDM3B as Specific Susceptibility for IDH2 and TET2 Mutant Genotypes Background and Significance Clonal Hematopoiesis (CH) refers to the abnormal growth of genetically distinct subclones of cells initiated by specific mutations in Hematopoietic Stem Cells (HSCs). This phenomen...

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

This is an academic paper report on the study of acute myeloid leukemia (AML) stem cells. The study found that venetoclax treatment targeting the BCL-2 protein induces different mitochondrial calcium signaling changes in drug-sensitive and drug-resistant AML stem cells, thereby affecting their oxidative phosphorylation metabolism and survival. The ...

Mechanisms of Response and Tolerance to Active RAS Inhibition in KRAS-Mutant NSCLC

Response and Resistance Mechanisms of RAS Inhibitors in KRAS-Mutant NSCLC Research Background With the clinical development of RAS inhibitors, the treatment of KRAS-mutant Non-Small Cell Lung Cancer (NSCLC) faces a new turning point. However, in clinical practice, patients show poor long-term responses to RAS inhibitors, influencing clinical effica...

High-Throughput Discovery of MHC Class I- and II-Restricted T Cell Epitopes Using Synthetic Cellular Circuits

High-Throughput Discovery of MHC Class I and II Restricted T Cell Epitopes Using a Novel Synthetic Cellular Circuit Research Background and Issues In recent years, antigen discovery technologies have made remarkable progress, especially in the application of human T-cell receptors (TCRs) in the recognition of major histocompatibility complex (MHC) ...