PLX4720 / Daiichi Sankyo - LARVOL DELTA

A migrasome-related LncRNA signatures for predicting prognosis and immunotherapeutic response in colorectal cancer. (PubMed, Sci Rep) - "In addition, drug sensitivity screening revealed that high-risk patients were more likely to resist current targeted drugs including PLX-4720 and JAK-8517 than low-risk patients. This study identifies a novel migrasome-related lncRNA signature as a reliable prognostic tool for CRC, highlighting its potential in patient stratification and personalized therapy."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

BRAF inhibition increases TGFβ2 production and stimulates metastasis in mice with endogenous BRAFV600E-induced hepatocellular carcinoma. (PubMed, Proc Natl Acad Sci U S A) - "While the BRAF inhibitor PLX4720 effectively reduced primary tumors and extended survival, it paradoxically increased sarcomatoid metastases...We conclude that BRAFV600E drives diverse primary tumors but only one type of metastasis and that RAF inhibition, while effective against primary tumors, may promote metastasis through TGFβ2-mediated EMT. Although RAF inhibitors remain promising therapies, their unintended role in enhancing metastasis raises concerns that may extend beyond liver cancer to other BRAFV600E-driven malignancies."

Journal • Preclinical • Hepatocellular Cancer • Hepatology • Liver Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • CDKN2A • TGFB1 • TGFB2 • TP53

Identification and validation of prognostic genes associated with m6A-regulated programmed cell death in acute lymphoblastic leukemia. (PubMed, Sci Rep) - "Sensitivity analysis of 60 chemotherapy agents indicated that Bicalutamide was more effective in LRG, while ATRA, CCT018159, PHA-665752, and PLX4720 demonstrated greater efficacy in HRG. RT-qPCR validation confirmed upregulation of CDK4 and downregulation of CFLAR in ALL samples (P < 0.05). This study offers important theoretical support for the prognostic evaluation and personalized treatment strategies in ALL."

Biomarker • Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CDK4 • CFLAR

scGSDR: Harnessing gene semantics for single-cell pharmacological profiling. (PubMed, Commun Biol) - "Literature review of top-ranking genes in predictions such as BCL2, CCND1, and PIK3CA for PLX4720 confirmed their relevance. Overall, scGSDR, by incorporating gene semantics, enhances predictive modeling of cellular responses to diverse drugs, proving invaluable for scenarios involving both single drug and combination therapies and effectively identifying key resistance-related pathways, thus advancing precision medicine and targeted therapy development."

Journal • BCL2 • CCND1 • PIK3CA

Gadd45B Deficiency Drives Radio-Resistance in BRAFV600E-Mutated Differentiated Thyroid Cancer by Disrupting Iodine Metabolic Genes. (PubMed, Cancers (Basel)) - "Gadd45B plays a pivotal role in regulating the differentiation status and RAI sensitivity of BRAFV600E-mutated thyroid cancer. These findings identify Gadd45B as a promising therapeutic target for restoring RAI responsiveness in RAIR-DTC patients."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • GADD45B • MYC

Characterization and inhibitor sensitivity of ARAF, BRAF, and CRAF kinases. (PubMed, J Biol Chem) - "Type I inhibitor SB590885 is roughly equipotent across RAF isoforms and, as expected, type I.5 inhibitors are typically most potent against BRAFV600E. Crystal structures of CRAF in complex with type I.5 inhibitor PLX4720 reveal an asymmetric CRAF dimer with one CRAF subunit bound in the inactive state and the second bound in an αC-helix-in, active conformation with an altered inhibitor pose. Our findings have important implications for understanding the pharmacology of current RAF inhibitors and will inform development of new agents with distinct isoform selectivity."

Journal • Melanoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • ARAF • BRAF

TRP-related gene signatures predict survival and the immune microenvironment in rectal cancer: a comprehensive bioinformatics study. (PubMed, Front Immunol) - "Furthermore, several targeted drugs, including MK-2206, pazopanib, JNK inhibitor VIII, PLX4720, and NU-7441, were associated with risk scores. This study identified five TRP-related biomarkers associated with RC prognosis, providing novel insights into the role of TRP channels in RC development. These findings may contribute to a deeper understanding of RC pathogenesis and offer potential targets for personalized therapy."

Biomarker • Gene Signature • Journal • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor • CD8 • GLTP

Characterization and inhibitor sensitivity of ARAF, BRAF, and CRAF complexes. (PubMed, bioRxiv) - "Type I inhibitor SB590885 is roughly equipotent across RAF isoforms and, as expected, type I.5 inhibitors are typically most potent against BRAFV600E. Crystal structures of CRAF in complex with type I.5 inhibitor PLX4720 reveal an asymmetric CRAF dimer with one CRAF subunit bound in the inactive state and the second bound in an aC-helix-in, active conformation with an altered inhibitor pose. Our findings have important implications for understanding the pharmacology of current RAF inhibitors and will inform development of new agents with distinct isoform selectivity."

Journal • Melanoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • ARAF • BRAF

Identification of anoikis-related genes to develop a risk model and predict the prognosis and tumor microenvironment in rectal adenocarcinoma. (PubMed, Front Genet) - "Drug sensitivity analysis revealed differences in the IC50 values of OSI-027, PLX-4720, UMI-77, and Sapitinib between the high-risk and low-risk groups. Enrichment analysis revealed that these prognostic ARGs were primarily enriched in pathways and biological processes related to tumorigenesis. The risk model of ARGs can effectively predict READ prognosis and provide potential therapeutic targets."

Biomarker • Journal • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Solid Tumor • ALDH1A1 • BRCA1 • KRT17

Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells. (PubMed, Cancer Chemother Pharmacol) - "Taken together, this study provides the first experimental evidence to demonstrate that all G12 mutation cell lines are sensitive to VS6766 applied either alone or combined with 5-FU or AKT inhibitor."

Journal • Colorectal Cancer • Oncology • Solid Tumor • KRAS

Dissecting Branch-Specific Unfolded Protein Response Activation in Drug-Tolerant BRAF-Mutant Melanoma using Data-Independent Acquisition Mass Spectrometry. (PubMed, Mol Cell Proteomics) - "These targets were subsequently applied to investigate proteomic changes in multiple BRAF-mutant melanoma cell lines treated with a BRAF inhibitor (PLX4720, i.e., vemurafenib). Our findings revealed differential regulation of the XBP1s branch of the UPR in the BRAF-mutant melanoma cell lines after PLX4720 treatment, likely due to calcium activation, suggesting that the UPR plays a role as a non-genetic mechanism of drug tolerance in melanoma. In conclusion, the validated branch-specific UPR proteomic targets identified in this study provide a robust framework for investigating this pathway across different cell types, drug treatments, and disease conditions in a high-throughput manner."

Journal • CNS Disorders • Diabetes • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • ATF6 • BRAF • ERN1

KDM6A Regulates Sex Specific Immune Responses in Melanoma. (EACR 2025) - "In mice fed chow containing the Braf inhibitor PLX4720, control tumour growth was relatively constrained, however this effect was abrogated by the loss of Kdm6a... Collectively our results support a tumour suppressive role for KDM6A in melanoma, that is particularly prominent in women compared to men and may influence responses to treatment. Understanding these subtleties may improve outcomes for both sexes."

IO biomarker • Melanoma • Oncology • Solid Tumor • CD8 • KDM6A

A bioinformatics-driven approach to identify biomarkers and elucidate the pathogenesis of type 2 diabetes concurrent with pulmonary tuberculosis. (PubMed, Sci Rep) - "Seven drugs (ERK_440_1713, JAK_8517_1739, Palbociclib_1054, PLX.4720_1036, Savolitinib_1936, Selumetinib_1736, and VX.11e_2096) exhibited significant sensitivity in patients with high-expression or low-expression of C1QA. Five genes (C1QA, MMP8, MMP9, CD248, and LINC00278) have potential as diagnostic markers for PTB + T2DM, and three genes (C1QA, MMP8, and MMP9) were upregulated in the peripheral blood of PTB + T2DM patients. Our findings may serve as a valuable reference for future research and clinical applications."

Biomarker • Journal • Diabetes • Infectious Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Tuberculosis • Type 2 Diabetes Mellitus • C1QA • CEACAM8 • COL1A2 • IL17A • MAPK4 • MIR25 • MIR363 • MIR671 • MIR942 • MMP8 • MMP9

Understanding how treatment responses alter the myeloid compartment in BRAF-mutant melanoma (IMMUNOLOGY 2025) - "To investigate this, we employed a tamoxifen-inducible engrafted skin model of melanoma driven by BRAFV600E expression and Pten loss (Braf/Pten model)...We now show that the addition of the synthetic triterpenoid CDDO-Me to the BRAFi PLX4720 arrested resistance and significantly reduced tumor burden...Consistent with this, we identified alterations in myeloid cell recruitment and subset activation during the development of BRAFi resistance using scRNA-seq and flow cytometry. Collectively, these findings indicate that CDDO-Me may impede the development of BRAFi resistance and support its role in novel combination therapies for melanoma.Keywords: Animals Human Rodent; Cells Monocytes/Macrophages; Molecules Cell Surface Molecules; Tissues Skin"

Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF • PTEN

Targeting TGFBR2 neddylation suppresses metastatic/immunosuppressive abilities and enhances responsiveness to BRAF inhibitor in melanoma with BRAF V600E mutation (AACR 2025) - "This study explores whether targeting TGFBR2 neddylation suppresses metastasis/immunosuppression and enhances BRAF inhibitor response. Gene Set Enrichment Analysis (GSEA) was performed to predict the possible pathways suppressed by the treatment with the protein neddylation inhibitor MLN4924 in melanoma cells. Our data suggest that targeting TGFBR2 neddylation might be a novel strategy to combat the metastatic/immunosuppressive and BRAF inhibitor-resistant melanoma with BRAF V600E mutation."

Metastases • Melanoma • Oncology • Solid Tumor • NEDD8 • TGFB1 • TGFBR2

Dissecting Branch-Specific Unfolded Protein Response Activation in Drug-Tolerant BRAF-Mutant Melanoma using Data-Independent Acquisition Mass Spectrometry. (PubMed, bioRxiv) - "These targets were subsequently applied to investigate proteomic changes in multiple patient-derived BRAF-mutant melanoma cell lines treated with a BRAF inhibitor (PLX4720, i.e., vemurafenib). Our findings revealed differential regulation of the XBP1s branch of the UPR in the BRAF-mutant melanoma cell lines after PLX4720 treatment, likely due to calcium activation, suggesting that the UPR plays a role as a non-genetic mechanism of drug tolerance in melanoma. In conclusion, the validated branch-specific UPR proteomic targets identified in this study provide a robust framework for investigating this pathway across different cell types, drug treatments, and disease conditions in a high-throughput manner."

Journal • CNS Disorders • Diabetes • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • ATF6 • BRAF • ERN1

The Role of Coagulation-Related Genes in Glioblastoma: A Comprehensive Analysis of the Tumor Microenvironment, Prognosis, and Treatment. (PubMed, Biochem Genet) - "The CRG-based risk signature model effectively predicts the prognosis of GBM patients and aids in assessing the efficacy of ICI therapy and chemotherapy. Furthermore, the genes LEFTY2, SERPINC1 and the drug PLX4720 offer potential directions for the development of novel therapeutic strategies for GBM."

Biomarker • IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Infectious Disease • Oncology • Solid Tumor • MMP2 • SPP1

Subtype cluster analysis unveiled the correlation between m6A- and cuproptosis-related lncRNAs and the prognosis, immune microenvironment, and treatment sensitivity of esophageal cancer. (PubMed, Front Immunol) - "Furthermore, nine candidate drugs with potential therapeutic efficacy in EC were identified: Bleomycin, Cisplatin, Cyclopamine, PLX4720, Erlotinib, Gefitinib, RO.3306, XMD8.85, and WH.4.023. Furthermore, it identifies potential therapeutic agents with efficacy against EC. These findings hold significant promise for enhancing the survival of EC patients and provide valuable insights to inform clinical decision-making in the management of this disease."

Biomarker • IO biomarker • Journal • Esophageal Cancer • Oncology • CD40 • CD40LG • ELF3 • HHLA2 • HNF1A • LGALS9 • MIR181A1 • TNFRSF14 • TNFRSF18 • TNFSF15

Genome-wide transcriptome analysis and drug target discovery reveal key genes and pathways in thyroid cancer metastasis. (PubMed, Front Endocrinol (Lausanne)) - "Application of aspirin, a TXA2 inhibitor, significantly reduced lung metastases...Braf-mutant Met cells developed resistance to BRAFV600E inhibitor PLX4720, but remained sensitive to β-catenin inhibitor PKF118-310. We have identified several overexpressed genes/pathways in thyroid cancer metastasis, making them attractive therapeutic targets. Given the complexity of metastasis involving multiple pathways (PD-L1, Mertk, IL6, COX-1/Tbxas1-TXA2), simultaneously targeting more than one of these pathways may be warranted to achieve better therapeutic effect for metastatic thyroid cancer."

IO biomarker • Journal • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Follicular Carcinoma • Thyroid Gland Papillary Carcinoma • AXL • CCL11 • CCL2 • CTNNB1 • CXCL5 • IL5 • IL6 • MERTK

Combinatorial Targeting of Common Docking and ATP Binding Sites on Mps1 MAPK for Management of Pathogenic Fungi. (PubMed, J Agric Food Chem) - "In vivo assays demonstrated that TAK-733 exhibits combinational effects with ATP-competitive inhibitors PLX-4720 and A378-0. Collectively, we present TAK-733 as having a new mechanism of action suitable for combinational application with ATP-competitive inhibitors in the management of pathogenic fungi."

Journal • MAP2K1

A Novel Mitochondrial-Related Gene Signature for the Prediction of Prognosis and Therapeutic Efficacy in Lower-Grade Glioma. (PubMed, Biochem Genet) - "Finally, using data from the CTRPv2 and GDSC2 datasets to assess chemotherapy response in LGG, it was predicted that the chemotherapeutic agents AZD6482, MG-132, and PLX-4720 might be potential agents for patients in the high-MiAS group of LGG. In contrast, overexpression of OCIAD2 enhanced these abilities of glioma cells. This study found that MRGs were correlated with LGG patient prognosis, which is expected to provide new treatment strategies for LGG patients with different MiAS."

Gene Signature • IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Involvement of ICAM5 in Carcinostasis Effects on LUAD Based on the ROS1-Related Prognostic Model. (PubMed, J Inflamm Res) - "PLX4720 may be a suitable treatment for the high-risk patient population...Personalized therapy may play an essential role in treatment. We further investigated the role of ICAM5 in inhibiting the malignant bioactivity of LUAD cells."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ICAM5 • ROS1

BrafV600E-induced cancer inflammation in a mouse model of thyroid tumorigenesis (ESMO 2024) - "To investigate reversibility of the inflammatory response to BrafCA/+ activation, mutant mice aged 6 months were fed with Braf kinase inhibitor Vemurafenib (PLX4720) or control dietary pellets for 4 weeks. All cytokines showed a gradual increase of gene expression between age 1 to 6 months in non-induced mutant mice, and a subsequent decrease at 12 months. Inflammatory response due to Braf activation is an early event in thyroid carcinoma development, with a time-course dependent expression pattern. Targeted Braf inhibition significantly down-regulates cytokine expression."

IO biomarker • Preclinical • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • IL1B • IL6 • TNFA

CTHRC1 is associated with BRAF(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma. (PubMed, Biomol Biomed) - "Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma."

Immune cell • IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

The ERK5 pathway in BRAFV600E melanoma cells plays a role in development of acquired resistance to dabrafenib but not vemurafenib. (PubMed, FEBS Lett) - "We investigated the role of the ERK5 pathway in BRAFV600E melanoma cells and cells with acquired resistance to PLX4720 (vemurafenib) and dabrafenib. However, in dabrafenib-resistant cells, ERK5 inhibition reduced viability and enhanced the anti-proliferative effect of MEK1/2 inhibition. Targeting the ERK5 pathway may represent a therapeutic opportunity in dabrafenib-resistant melanoma."

Journal • Preclinical • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor