motesanib (AMG 706) / Amgen, Takeda - LARVOL DELTA

Bioinformatics-based identification of ferroptosis-related biomarkers and immune infiltration in retinoblastoma. (PubMed, Transl Cancer Res) - "Drug sensitivity analysis suggested AUY922, AG.014699, and AMG.706 as candidate therapeutic agents. This study identified three ferroptosis-related genes (FRGs) as potential diagnostic biomarkers of RB. Their association with immune cell infiltration provides new insights into the molecular mechanisms of RB and highlights potential therapeutic opportunities."

Biomarker • Journal • Eye Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • HSPB1 • NFE2L2

TrxR1 inhibition sensitizes hepatocellular carcinoma to Motesanib via an autophagy-ROS-JNK/ER stress axis. (PubMed, Biol Direct) - "This orchestrated stress response subsequently led to sustained endoplasmic reticulum (ER) stress and JNK pathway activation, culminating in DNA damage, impaired proliferation, and reduced cell viability. Taken together, our results identify the combination of MOT and AF as a promising and mechanistically grounded treatment regimen for advanced HCC (Graphical Abstract)."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • ATG5

CREB–mediated pharmacologic antagonism is associated with adaptive escape from MAPK inhibition in melanoma (SID 2026) - "To identify antagonistic compounds, we subjected 5 BRAF* melanoma lines to a high-throughput screen of 1,600 broad-spectrum FDA-approved and advanced preclinical drugs, co-administered with dabrafenib + trametinib (D+T; 4.0/0.4 nM)...The top 5 ranking antagonistic drugs were Mocetinostat (E=0.92), CP673451 (E=0.88), Axitinib (E=0.76), Amuvatinib (E=0.74), and BX-795 (E=0.74)...Notably, this subset included 14 mechanistically related platelet-derived growth factor receptor inhibitors (PDGFRI: CP673451, Amavadin, Axitinib, Crenolanib, Nintedanib, Sorafenib, Linifanib, Tivozanib, Imatinib, Masitinib, Pazopanib, Motesanib, Sunitinib)...Comparative phosphokinome profiling across the 3 cell lines identified CREB phosphorylation at S133 as a conserved event, robustly suppressed by D+T but selectively rescued by PDGFRi co-treatment. Together, these data identify PDGFR inhibitors as a reproducible source of antagonism to BRAF+MEK-targeted therapy and nominate CREB phosphorylation..."

Melanoma • Solid Tumor

In Silico Molecular Docking and Pharmacokinetic Evaluation of Cannabinoid Derivatives as Multi-Target Inhibitors for EGFR, VEGFR-1, and VEGFR-2 Proteins. (PubMed, Curr Issues Mol Biol) - "Among these, 2'-Hydroxy-Delta (9)-THC and Ajulemic Acid combined favorable multi-target binding with superior predicted pharmacokinetic properties compared with other cannabinoids and reference inhibitors (lapatinib, motesanib, and sorafenib). Toxicity predictions classified all compounds as moderately toxic, with Ajulemic Acid showing a comparatively more favorable safety profile. These findings do not demonstrate biological inhibition and should be interpreted strictly as hypothesis-generating computational evidence, providing a rational framework for future in vivo and in vitro validations."

Journal • PK/PD data • Oncology • EGFR • FLT1 • KDR

Multiomics profiling Identifies MCMBP as a prognostic biomarker and a potential immune-related target in pancreatic ductal adenocarcinoma via the JAK-STAT3 pathway. (PubMed, Front Immunol) - "High MCMBP expression was ass-ociated with sensitivity to Gemcitabine combined with Paclitaxel, as well as small mo-lecules such as Tozasertib and Motesanib. Overexpression of MCMBP may serve as a prognostic biomarker and p-otential therapeutic target in PAAD. It drives PAAD progression by activating the JAK-STAT3 pathway to upregulate PD-L1."

Biomarker • IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD4

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

SUMOylation-regulated genes in colon cancer: expression patterns and clinical implications. (PubMed, Discov Oncol) - "Nomoscore-high patients exhibited resistance to AMG.706 and ABT.888, suggesting therapeutic vulnerabilities. These findings highlight SUMOylation plays a critical role in CRC heterogeneity, immune modulation, and prognosis, offering a novel biomarker system for risk stratification and personalized therapy."

Journal • Colon Cancer • Colorectal Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • GJB6

Glycolysis-Driven Prognostic Model for Acute Myeloid Leukemia: Insights into the Immune Landscape and Drug Sensitivity. (PubMed, Biomedicines) - "Drug sensitivity analysis showed that high-risk patients exhibited resistance to crizotinib and lapatinib but were more sensitive to motesanib. Combined with immune microenvironment analysis and drug sensitivity analysis, we screened metabolic characteristics and identified an immune signature to provide deeper insight into AML. Our findings may assist in identifying new therapeutic targets and more effective personalized treatment regimes."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD73 • NT5E • TFF3

Systematic multiomics analysis and in vitro experiments suggest that ITGA5 could serve as a promising therapeutic target for ccRCC. (PubMed, Cancer Cell Int) - "Our findings clarified the adverse outcome induced by high expression of ITGA5 in ccRCC patients. In vitro experiments and bioinformatical analysis identified ITGA5 function as predominantly cell proliferation, migration, angiogenesis, and macrophage recruitment. Further, we predicted immune infiltration and medication sensitivity regulation by ITGA5 and proposed a joint use of ITGA5 inhibitors and anti-angiogenetic drugs as a potential potent therapeutic strategy."

Journal • Preclinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD8 • ITGA5 • VHL

Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data. (PubMed, Phenomics) - "Sensitivity analysis of common chemotherapeutic drugs showed that high expression of CALU could sensitize chemotherapeutic drugs such as 5Z-7-Oxozeaenol, AMG-706 and Cytarabine, but could lead to drug resistance to chemotherapeutic drugs such as Embelin, Salubrinal and Tipifarnib. Thus, our results indicate that CALU could be a biomarker and designing personalized treatment approaches for ccRCC patients. The online version contains supplementary material available at 10.1007/s43657-024-00169-7."

Heterogeneity • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD4 • CD8

Construction and clinical significance of prognostic risk markers based on cancer driver genes in lung adenocarcinoma. (PubMed, Clin Transl Oncol) - "This study identified 11 effective biomarkers, DE-CDGs, which can predict LUAD prognosis and explored the biological significance of CDGs in LUAD prognosis, immunotherapy, and treatment."

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

ELF4 was a prognostic biomarker and related to immune infiltrates in glioma. (PubMed, J Cancer) - "Molecular docking analysis revealed ELF4 might be targeted by drugs/compounds, including Veliparib (ABT-888), Motesanib (AMG 706), and EHT 1864. Genomic analysis revealed that, in LGG, in the low ELF4 expression subgroup, IDH1 demonstrated a higher mutation rate, and TP53 and ATRX Chromatin Remodeler (ATRX) displayed the lower mutation rates, than the high ELF4 expression group. Our research suggests that ELF4 may contribute to the prognostic assessment of glioma and personalized medicine."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • ATRX • IDH1 • IFNA1 • IL2 • IL6 • STAT5 • STAT5AWqe • TP53

Comprehensive analyses of mitophagy-related genes and mitophagy-related lncRNAs for patients with ovarian cancer. (PubMed, BMC Womens Health) - "Our study revealed the roles of MRLs and MRL-model in expression, prognosis, chemotherapy, immunotherapy, and molecular mechanism of OC. Our findings were able to stratify OC patients with high risk, unfavorable prognosis and variant treatment sensitivity, thus improving clinical outcomes for OC patients."

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

ANRGs impact on gastric cancer progression and drug efficacy: A comprehensive study. (PubMed, Medicine (Baltimore)) - "The half maximal inhibitory concentration (IC50) values of Ponatinib (ap.24534), Motesanib (amg.706), and Navitoclax (abt.263) were lower in the high-risk group, indicating that patients in the high-risk group were more sensitive to these chemotherapy drugs, meaning with better clinical outcomes. Our study identified key genes based on ANRGs and developed a novel gene signature for predicting the prognosis of GC patients and understanding the relationship between immunity and tumor mutation burden. Additionally, we identified chemotherapeutic drugs that can guide GC treatment and elucidated the binding affinity between specific targeted drugs and distinct protein sites, providing novel insights for the precise treatment of GC patients."

Journal • Tumor mutational burden • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ANXA5 • CCN1 • EGF • TMB • ZBTB7A

A novel prognostic N-methylguanosine-related long non-coding RNA signature in clear cell renal cell carcinoma. (PubMed, Sci Rep) - "High-risk group of patients was more susceptible to A.443654, A.770041, ABT.888, AMG.706, and AZ628. Quantitative real-time polymerase chain reaction (qRT-PCR) exhibited that the expression levels of LINC01507, AC093278.2 were very high in all five ccRCC cell lines, AC084876.1 was upregulated in all ccRCC cell lines except 786-O, and the levels of AL118508.1 and DUXAP8 were upregulated in the Caki-1 cell line. This risk model may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with ccRCC."

IO biomarker • Journal • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • DUXAP8 • TMB

A novel stratification framework based on anoikis-related genes for predicting the prognosis in patients with osteosarcoma. (PubMed, Front Immunol) - "The low-risk group was sensitive to the immune checkpoint PD-1 inhibitor, and the high-risk group exhibited lower inhibitory concentration values by 50% for 24 drugs, including AG.014699, AMG.706, and AZD6482. The prognostic stratification framework of patients with OS based on ARGs, such as BNIP3 and CXCL12, may lead to more efficient clinical management."

IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCL12

Predicting response of immunotherapy and targeted therapy and prognosis characteristics for renal clear cell carcinoma based on m1A methylation regulators. (PubMed, Sci Rep) - ""pRRophetic" package screened five potential small molecule drugs (A.443654, A.770041, ABT.888, AG.014699, AMG.706). Finally, polymerase chain reaction (PCR) showed the expression of YTHN6-Methyladenosine RNA Binding Protein 1[YTHDF1], TRNA Methyltransferase 61B [TRMT61B], TRNA Methyltransferase 10C [TRMT10C] and AlkB Homolog 1[ALKBH1] in ccRCC cell lines. To sum up, the prognosis risk model we created not only has good predictive value, but also can provide guidance for accurately predicting the prognosis of ccRCC."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Rectal Cancer • Renal Cell Carcinoma • Solid Tumor • EGFR • ER • YTHDF1

A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer. (PubMed, Front Pharmacol) - "Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype...Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression. A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TGFB1

[VIRTUAL] Oral VEGFR Inhibitor Monotherapy for Lung Cancer: Should We or Should We Not? (IASLC-WCLC 2020) - P3 | "Carboplatin plus paclitaxel combined with bevacizumab has been established as a first-line therapy for patients with advanced non-squamous NSCLC...Docetaxel plus nintedanib has become a second-line treatment for patients with adenocarcinomas. When added to first-line chemotherapy, neither sorafenib nor motesanib improved overall survival of patients...Vandetanib failed to improve overall survival compared to placebo in patients with advanced NSCLC who had been pretreated with an EGFR tyrosine kinase inhibitor and one or two chemotherapy regimens (4)...Sunitinib as maintenance therapy improved progression-free survival but had no impact on survival of patients with advanced NSCLC (6)...Apatinib, an inhibitor of VEGFR-2, has also shown efficacy in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs (8)...The LEAP-007 phase 3 trial (NCT03829332) compares pembrolizumab plus lenvatinib to pembrolizumab plus placebo in treatment-naïve patients..."

IO biomarker • Monotherapy • Anorexia • Cardiovascular • Dyslipidemia • Fatigue • Heart Failure • Hypertension • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FGFR • FGFR1 • FLT1 • KIT • PD-L1 • RET

Effect of topical motesanib in experimental corneal neovascularization model. (PubMed, Int Ophthalmol) - "Motesanib with a dose of 7.5 mg/ml statistically significantly suppressed the VEGFR-2 mRNA level compared with other treatment doses and may be more effective than bevacizumab. Further, miRNA-126 can be used as a proangiogenic marker."

Journal • Review • Anesthesia • KDR • MIR21

Angiogenesis-related gene signatures reveal the prognosis of cervical cancer based on single cell sequencing and co-expression network analysis. (PubMed, Front Cell Dev Biol) - "First we screened the AG gene set from GeneCard website, and then performed angiogenesis-related scores (AGS) per cell from single cell sequencing dataset GSE168652, followed by performing weighted gene co-expression network analysis (WGCNA) for cervical cancer patients according to angiogenesis phenotype...Patients in the low-AGS group were more sensitive to AMG.706, Bosutinib, and Lenalidomide while Imatinib, Pazopanib, and Sorafenib were more recommended to patients in the high-AGS group...Meanwhile, the results showed that TXNDC12 promoted the migration of cervical cancer cells and the tubule-forming ability of endothelial cells. In conclusion, our model based on genes with AG features can effectively assess the prognosis of cervical cancer, and can also provide reference for clinicians to choose immune-related treatments."

Gene Signature • Journal • Tumor mutational burden • Cervical Cancer • Gynecologic Cancers • Immune Modulation • Inflammation • Oncology • Solid Tumor • TMB

The Expression of ARMCX1 in Gastric Cancer Contributes to Prognosis and Influences Chemotherapy. (PubMed, J Immunol Res) - "Among which, ARMCX1 exhibited great potential to serve as a prognostic biomarker for gastric patients; furthermore, patients with low expression of ARMCX1 could be more sensitive to these 9 chemotherapeutic agents: A-770041, AMG-706, ATRA, BEZ235, bortezomib, CGP60474, dasatinib, HG-64-1, and pazopanib, rather than the other chemotherapeutic agents. This study helps the improvement of evaluating the prognosis of gastric cancer patients, and would help optimize chemotherapeutic strategies in consideration of the expression of ARMCX1."

Biomarker • Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A meta-analysis of the efficacy and toxicity of tyrosine kinase inhibitors in treating patients with different types of thyroid cancer: how to choose drugs appropriately? (PubMed, Curr Opin Oncol) - "TKIs significantly prolonged progression-free survival and OS or improved ORR in patients with different types of TC (P < 0.01). Our recommendation is to select appropriate TKIs to treat different types of TC patients, and to prevent and manage drug-related AEs after using TKIs."

Journal • Retrospective data • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Comprehensive analysis of cuproptosis-related lncRNAs in the prognosis and therapy response of patients with bladder cancer. (PubMed, Ann Transl Med) - "The sensitivity of multiple antitumor drugs was negatively related to risk score, including AR-42, AS605240, FK866, TAK-715, and tubastatin A, while the sensitivity of some antitumor drugs, such as AMG-706, BX-795, and RO-3306, were positively correlated with risk score. Our study established and verified a novel clinical risk signature with cuproptosis-related lncRNAs that may predict therapy response and prognosis with robust and stable accuracy in patients with BLCA and enhance the personalized management of this patient population."

IO biomarker • Journal • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Urothelial Cancer • TMB

Identification of FERMT1 and SGCD as key marker in acute aortic dissection from the perspective of predictive, preventive, and personalized medicine. (PubMed, EPMA J) - "In addition, the drug-gene interaction network identified motesanib and pyrazoloacridine as potential therapeutic agents for two key markers, which may provide personalized medical services for AAD patients...In conclusion, our study provides a new perspective for developing a PPPM method for managing AAD patients. The online version contains supplementary material available at 10.1007/s13167-022-00302-4."

Journal • Immunology • Inflammation • FERMT1