motesanib (AMG 706)

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, especially for rare GIST subtypes.

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.

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.

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.

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.

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.

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.

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.

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.

"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.

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.

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.