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- bimiralisib (PQR309) / PIQUR
Oral dual PI3K/mTOR inhibitor bimiralisib demonstrates tolerability and a signal of activity in head and neck squamous cell cancer with NOTCH1 loss-of-function mutation (Board 109: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_378;
P2
Conclusion Bimiralisib was well tolerated and RP2D of 140 mg given orally twice weekly on Days 1 and 2 was selected for further studies. In agreement with our preclinical models, there was an encouraging activity in a SCCHN patient with NOTCH1 LoF mutation and this observation is now being validated in a proof-of-concept phase 2 study (NCT03740100).
- Opdivo (nivolumab) / Ono Pharma, BMS, Aliqopa (copanlisib) / Bayer
Phase IB combination study of copanlisib and nivolumab in advanced solid tumors and lymphomas (Board 105: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_375;
P1
Funded by NCI Contract No. HHSN261200800001E.
- taselisib (GDC-0032) / Roche
The p85b regulatory subunit of PI3K plays a unique role in taselisib-induced mutant p110a degradation () - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_372;
Furthermore, disruption of RTK/p85b interaction rescued the taselisib-mediated mutant p110a degradation. In summary, these studies indicate that the p85b regulatory subunit plays a unique role in taselisib-induced mutant p110a degradation, by recruiting p110a to the plasma membrane where it is ubiquitinated and subsequently degraded.
- JQ-1 / Roche, Zejula (niraparib) / GSK, J&J, Takeda
Computational models of synergy contribute to efficient combination screening (Board 141: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_181;
The tool successfully predicts synergy between niraparib and the SUMO inhibitor 2-D08, and niraparib and BCL2 inhibitors, which we observed in our screen. Conclusions Computational tools for synergy have predictive value and can be useful to prioritize libraries for empirical combination screening.
- Afinitor (everolimus) / Novartis
Drug screening and molecular profiling identifies INKA1 as a predictive biomarker for sensitivity to MAPK inhibition-antimitotic combination treatment in pancreatic ductal adenocarcinoma (Board 137: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_177;
The result therefore suggests that PAK4 activity is an important negative regulator of cell death triggered by the trametinib-vincristine combination. In summary, we identified trametinib + vincristine as a selective drug combination for a subset of KRAS-mutant PDAC with a putative predictive biomarker (INKA1 expression), which holds a potential for clinical translation, hence requires further exploration.
- Tafinlar (dabrafenib) / Novartis, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
HRASG12S mutant mediates resistance to a PI3K&[alpha] inhibitor CYH33 in esophageal squamous cell carcinomas (Board 116: Level 2 - Hall D) - Sep 18, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_155;
In summary, continuous treatment of CYH33 might induce genomic instability and HRASG12S mutant mediated resistance to CYH33 in ESCC cells. Combination of MAPK inhibitors with CYH33 are able to overcome resistance mediated by HRAS hyper-activation.
- ||| Clinical: We may disagree. Patients with ntrk had cell cycle genes, pi3k, mapk, and other tyrosine kinases as co alterations. So if you only look for fusions if DNA negative, fusions will be missed. But if you consider none of those pathways as drivers, then I guess you are ok. (Twitter) - Sep 18, 2019
- ||| Clinical: This may depend on definition of driver. But from about 13,500 samples in TCGA and St Jude PeCan, most NTRK fusions patients had coexisting alteration in cell cycle, pi3k pathway, MAPK or other tyrosine kinase. (Twitter) - Sep 18, 2019
- ||| Clinical: I guess it depends on how one defines a driver. Based on #MSKimpact data on 45K cases, we find NTRK fusions are mutually exclusive with other kinase fusions or hotspot mutations that activate MAPK signaling, i.e. strong “mitogenic” drivers. But not PI3K/AKT/MTOR, CDKs, TP53/RB... (Twitter) - Sep 18, 2019
- | Clinical, Journal: Stage-dependent therapeutic efficacy in PI3K/mTOR-driven squamous cell carcinoma of the skin. (Pubmed Central) - Sep 18, 2019
Mechanistically, the resistant SCCs displayed increased miR-21 expression in mice and humans where antagonists of miR-21 rescued expression levels of GRHL3/PTEN, but the combination of miR-21 antagonism with PI3K/mTOR inhibition resulted in acquired SCC resistance in part via c-MYC and OCT-4 upregulation. In conclusion, our data provide molecular evidence for the efficacy of targeting oncogenic drivers of SCC during the initiation and promotion stages and indicate that combination therapy may induce an aggressive phenotype when applied in the establishment stage.
- | doxorubicin hydrochloride / generics
Journal: Phosphoinositide 3-Kinase Gamma Inhibition Protects from Anthracycline Cardiotoxicity and Reduces Tumor Growth. (Pubmed Central) - Sep 18, 2019
Anthracyclines, such as doxorubicin (DOX), are potent anticancer agents for the treatment of solid tumors and hematologic malignancies...Finally, PI3Kγ blockade in models of mammary gland tumors prevented DOX-induced cardiac dysfunction, and concomitantly synergized with the anti-tumor action of DOX, by unleashing anticancer immunity. Conclusions -Blockade of PI3Kγ may provide a dual therapeutic advantage in cancer therapy, by simultaneously preventing anthracyclines cardiotoxicity and reducing tumor growth.
- | pioglitazone / generics
Preclinical, Journal, IO Biomarker: PI3K/AKT/JNK/p38 signalling pathway-mediated neural apoptosis in the prefrontal cortex of mice is involved in the antidepressant-like effect of pioglitazone. (Pubmed Central) - Sep 18, 2019
In conclusion, our results showed that PI3K/AKT/JNK/p38 signalling pathway-mediated neural apoptosis in the PFC of mice may be involved in the antidepressant-like effect of pioglitazone. This provides novel insights into and therapeutic targets for inflammation-related depression.
- | Journal: Glucagon-like peptide-1 receptor regulates endoplasmic reticulum stress-induced apoptosis and the associated inflammatory response in chondrocytes and the progression of osteoarthritis in rat. (Pubmed Central) - Sep 18, 2019
In the end, liraglutide attenuated rat cartilage degeneration in an OA model of knee joints in vivo. Our results indicate that GLP-1R is a therapeutic target for the treatment of OA, and that liraglutide could be a therapeutic candidate for this clinical application.
- | Preclinical, Journal, PARP Biomarker, IO Biomarker: Association of cytosolic sialidase Neu2 with plasma membrane enhances Fas-mediated apoptosis by impairing PI3K-Akt/mTOR-mediated pathway in pancreatic cancer cells. (Pubmed Central) - Sep 18, 2019
To the best of our knowledge, this is the first report of cytosolic Neu2 on membrane, its association with Fas, enhanced desialylation, activation, and Fas-mediated apoptosis. Taken together, our study ascertains a novel concept by which the function of Fas/CD95 could be modulated indicating a critical role of upstream Neu2 as a promising target for inducing apoptosis in pancreatic cancer.
- | sirolimus / generics
Journal: Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors. (Pubmed Central) - Sep 18, 2019
Resistance to PI3K inhibitors correlated with the increased abundance of Skp2, ubiquitylation of AKT, cell proliferation in culture, and xenograft tumor growth in mice. These findings reveal a ubiquitin signaling feedback mechanism by which PI3K inhibitor resistance may emerge in aggressive breast cancer cells.
- | cisplatin / generics
Biomarker, Journal: Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via activating AXL/PI3K/Akt/NF-κB signaling pathway. (Pubmed Central) - Sep 18, 2019
DANCR promotes cisplatin resistance via activating AXL/PI3K/Akt/NF-κB signaling pathway in glioma. Our data suggested that DANCR would be a potential biomarker for predicting cisplatin sensitivity and a therapeutic target for enhancing cisplatin efficacy in glioma.
- | U0126 / Promega
Journal: Cyanidin-3-o-β-Glucoside Induces Megakaryocyte Apoptosis via PI3K/Akt- and MAPKs-Mediated Inhibition of NF-κB Signalling. (Pubmed Central) - Sep 18, 2019
U0126 (Erk1/2 inhibitor), SB203580 (p38 MAPK inhibitor) and 740 Y-P (PI3K agonist) significantly reversed Cy-3-g-reduced phosphorylation of p65. Taken together, our data indicate that Cy-3-g induces megakaryocyte apoptosis via the inhibition of NF-κB signalling, which may play important roles in regulating thrombopoiesis.
- | quercetin (LY294002) / Eli Lilly
Journal: Downregulation of monocarboxylate transporter 1 inhibits the invasion and migration through suppression of the PI3K/Akt signaling pathway in human nasopharyngeal carcinoma cells. (Pubmed Central) - Sep 18, 2019
LY294002, a PI3K inhibitor, increased the inhibition of invasion and migration mediated by downregulation of MCT1 in CNE2Z cells. These findings collectively suggested that MCT1 might act as a new regulator to improve invasion and migration of NPC cells and be correlated with activating the PI3K/Akt pathway.
- ||||| Interview: Thanks @DunleavyKieron for a great interview on follicular lymphoma! Keep an eye out for the full interview on https://t.co/VvOHuwP4kC where Dr. Dunleavy speaks to the viability of watch-and-wait strategies, systemic therapies, and research being done with PI3K inhibitors (Twitter) - Sep 17, 2019
- ||| Clinical: Congrats to @DavidFajgenbaum and @CureCastleman - Our manuscript in JCI on targeting PI3K/AKT/mTOR in idiopathic multicentric Castleman disease just published with commentary! Supports upcoming clinical trial. https://t.co/LeflgUlv9E (Twitter) - Sep 17, 2019
- | dactolisib (RTB101) / Novartis, PureTech
Journal: Perfluorooctanoic acid induces migration and invasion and inhibits apoptosis through the PI3K/AKT signaling pathway in human rhabdomyosarcoma cells. (Pubmed Central) - Sep 17, 2019
The results obtained show that the PI3K/AKT signaling pathway is implicated in mediating the pro‑neoplastic effects of PFOA. The data suggests that PFOA is a carcinogen capable of promoting RD cell migration and invasion and inhibiting apoptosis through the PI3K/AKT signaling pathway.
- | Preclinical, Journal: Sorcin is involved during embryo implantation via activating VEGF/PI3K/Akt pathway in mice. (Pubmed Central) - Sep 16, 2019
The migratory and invasive properties of HUVECs were abrogated by anti-VEGF or by adding culture media from sorcin blocked EECs, which indicated that sorcin might mediate angiogenesis during implantation. Taken together, sorcin is involved in regulation of Ca+2-mediated angiogenesis via VEGF/PI3K/Akt pathway in endometrial cells and plays a crucial role in preparing the endometrium for implantation.
- | Journal, PD(L)-1 Biomarker, IO biomarker: Genomic Analyses Identify Recurrent Alterations in Immune Evasion Genes in Diffuse Large B Cell Lymphoma, Leg Type. (Pubmed Central) - Sep 16, 2019
Collectively, these data broaden our understanding of cutaneous DLBCLs and suggest novel therapeutic approaches (e.g. BRAF or PI3K inhibitors). Additionally, they suggest novel treatment paradigms, wherein DLBCL-LTs can be targeted with strategies (e.g. immune checkpoint blockers) currently being developed for genomically similar PCNSLs/PTLs.
- | Journal: The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes. (Pubmed Central) - Sep 16, 2019
Our findings suggest that the benefits of calcineurin inhibition in FSGS may be due, in part, to the suppression of ANLN and mTOR. Moreover, these studies illustrate that rational therapeutic targets for familial FSGS can be identified through biochemical characterization of dysregulated podocyte phenotypes.
- | Journal: Brachyury gene copy number gain and activation of the PI3K/Akt pathway: association with upregulation of oncogenic Brachyury expression in skull base chordoma. (Pubmed Central) - Sep 14, 2019
CONCLUSIONS Activation of the PI3K/Akt pathway and Brachyury copy number gain are strongly associated with Brachyury overexpression, which appears to be a key event in chordoma growth regulation. These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma.
- | Daliresp (roflumilast) / Allergan, AstraZeneca, Takeda, Zydelig (idelalisib) / Gilead
Journal: Synergistic targeting of the regulatory and catalytic subunits of PI3Kδ in mature B cell malignancies. (Pubmed Central) - Sep 14, 2019
These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma. These data demonstrate that roflumilast and idelalisib suppress PI3K by distinct mechanisms, explaining the basis for their synergism, and suggest that the repurposing of PDE4 inhibitors to treat BCR-dependent malignancies is warranted.
- | Journal: The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation. (Pubmed Central) - Sep 14, 2019
In conclusion, inflammation-induced TNF promotes hepatocellular CCR10 expression and downstream PI3K/Akt-mediated hepatocarcinogenesis. CCR10 appears to function as a linkage between TNF stimulation and downstream PI3K/Akt pathway activation and shows promise as a potential therapeutic target for inflammation-driven HCC.
- | Kinaction (masitinib) / AB Science
Journal: Tumor Necrosis Factor-α Is Required for Mast Cell-Mediated Host Immunity Against Cutaneous Staphylococcus aureus Infection. (Pubmed Central) - Sep 14, 2019
In addition, S. aureus-induced MC activation was dependent on the c-kit receptor-activated phosphoinositide 3-kinase (PI3K)/AKT/P65-nuclear factor (NF-κB) pathway, which was confirmed by treatment with Masitinib (a c-kit receptor inhibitor), Wortmannin (a PI3K inhibitor), and pyrrolidine dithiocarbamate (a NF-κB inhibitor), respectively. The present study identifies the critical role of MCs in the host defense against S. aureus infection.
- | cisplatin / generics
Preclinical, Journal, IO Biomarker: Mir-22-3p Enhances the Chemosensitivity of Gastrointestinal Stromal Tumor Cell Lines to Cisplatin through PTEN/PI3K/Akt Pathway. (Pubmed Central) - Sep 14, 2019
In addition, the mRNA and protein levels of PTENwere significantly increased in cells treated with both Mir-22-3p analogue and cisplatin (p<0.05), while the expression levels of PI3K and Akt were significantly decreased (p<0.05). Mir-22-3p overexpression can increase the chemosensitivity of cisplatin in human gastrointestinal stromal tumor cells by PTEN/PI3K/Akt pathway.
- | Journal: Lupeol suppresses migration and invasion via p38/MAPK and PI3K/Akt signaling pathways in human osteosarcoma U-2 OS cells. (Pubmed Central) - Sep 14, 2019
Lupeol also decreased uPA, MMP-2, MMP-9, and N-cadherin but increased VE-cadherin in U-2 OS cells. Based on these observations, we suggest that lupeol can be used in anti-metastasis of human osteosarcoma cells in the future.
- | quercetin (LY294002) / Eli Lilly
Journal: Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway. (Pubmed Central) - Sep 14, 2019
Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells. CONCLUSIONS OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3ß-ß/catenin pathway.
- | Review, Journal: PI3K/AKT/mTOR Signaling Regulates the Virus/Host Cell Crosstalk in HPV-Positive Cervical Cancer Cells. (Pubmed Central) - Sep 14, 2019
This review highlights our current knowledge about the oxygen-dependent crosstalk of the PI3K/AKT/mTOR signaling circuit with the HPV oncogenes and the phenotypic state of the host cell. Moreover, since the PI3K/AKT/mTOR pathway is considered to be a promising target for anticancer therapy, we discuss clinical implications for the treatment of HPV-positive cervical and head and neck squamous cell carcinomas.
- | Biomarker, Journal: Exogenous Let-7a-5p Induces A549 Lung Cancer Cell Death Through BCL2L1-Mediated PI3Kγ Signaling Pathway. (Pubmed Central) - Sep 13, 2019
Furthermore, aberrant expression of BCL2L1 significantly altered the expression of lung cancer biomarkers such as MYC, EGFR, and Vimentin. To sum up, these data demonstrate that exogenous let-7a-5p induces A549 lung cancer cell death through BCL2L1-mediated PI3Kγ signaling pathway, which may be a useful target for lung cancer treatment.
- | azacitidine / Generic Mfg.
Journal: Curcumin Inhibits Joint Contracture through PTEN Demethylation and Targeting PI3K/Akt/mTOR Pathway in Myofibroblasts from Human Joint Capsule. (Pubmed Central) - Sep 13, 2019
In conclusion, our data illustrate part of the mechanism of curcumin inhibition in joint contracture. These results support the hypothesis that curcumin may potentially be used as a novel candidate for the treatment of joint contracture.
- | Journal: Hypoxia-induced PIM kinase and laminin-activated integrin α6 mediate resistance to PI3K inhibitors in bone-metastatic CRPC. (Pubmed Central) - Sep 13, 2019
We further demonstrate that both pathways drive resistance to PI3K inhibitors in PTEN-negative tumors. These results provide preclinical evidence that combined inhibition of integrin α6β1 and PIM kinase in CRPC is required to overcome tumor microenvironment-mediated resistance to PI3K inhibitors in PTEN-negative tumors within the hypoxic and laminin-rich bone microenvironment.
- ||| PI3K review in cancer https://t.co/Ytgz8UQic4 (Twitter) - Sep 13, 2019
- | vistusertib (AZD2014) / AstraZeneca, AZD8186 / AstraZeneca
Biomarker, Journal: Combined inhibition of PI3Kβ and mTOR inhibits growth of PTEN null tumours. (Pubmed Central) - Sep 12, 2019
In vivo biomarker analysis revealed that the monotherapy and combination treatment consistently reduced similar biomarkers, while combination increased nuclear translocation of the transcription factor FOXO3 and reduction in glucose uptake. These data suggest that combining the PI3Kβ inhibitor AZD8186 and vistusertib has potential to be an effective combination treatment for PTEN null tumors.
- | Journal: Mechanisms behind resistance to PI3K Inhibitor treatment induced by the PIM kinase. (Pubmed Central) - Sep 12, 2019
Importantly, PIM also controls NAD(P)H production by increasing glucose flux through the pentose phosphate shunt decreasing ROS production, and thereby diminishing the cytotoxicity of PI3K-AKT inhibitors. Treatment with PIM kinase inhibitors reverses this resistance phenotype making tumors increasingly susceptible to small molecule therapeutics which block the PI3K-AKT pathway.
- | Journal: Discovery of a natural PI3Kδ inhibitor through virtual screening and biological assay study. (Pubmed Central) - Sep 12, 2019
Docking studies showed that Glu826, Val827 and Val828 were key amino acid residues for PI3Kδ inhibitory activity. Ginkgoneolic acid may be a potential lead compound for developing effective and safe PI3Kδ-inhibiting drugs.
- | quercetin (LY294002) / Eli Lilly
Journal: Decreased PKG transcription mediated by PI3K/Akt/FoxO1 pathway is involved in the development of nitroglycerin tolerance. (Pubmed Central) - Sep 12, 2019
ROS production was significantly increased in NTG tolerant arteries, which was not be affected by LY294002 but inhibited by N-acetyl-L-cysteine. In conclusion, the present study suggests that PI3K/Akt in vascular smooth muscle is involved in the development of NTG tolerance via inhibiting PKG transcription and the effect is mediated by FoxO1.
- | Preclinical, Journal: Diosmetin Suppresses Neuronal Apoptosis and Inflammation by Modulating the Phosphoinositide 3-Kinase (PI3K)/AKT/Nuclear Factor-κB (NF-κB) Signaling Pathway in a Rat Model of Pneumococcal Meningitis. (Pubmed Central) - Sep 12, 2019
In the rat hippocampal tissue, levels of Akt, PI3K, MyD88 and NF-kappaB, and the number of TUNEL-positive apoptotic cells were significantly reduced in the diosmetin-treated group compared with negative control group (p<0.01). In a rat model of bacterial meningitis due to S. pneumoniae, diosmetin reduced neuroinflammation, and neuronal apoptosis by modulating the PI3K/AKT/NF-kappaB signaling pathway.
- | Journal: High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells. (Pubmed Central) - Sep 12, 2019
CONCLUSIONS Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.
- | Biomarker, Journal, IO Biomarker: Ferruginol Diterpenoid Selectively Inhibits Human Thyroid Cancer Growth by Inducing Mitochondrial Dependent Apoptosis, Endogenous Reactive Oxygen Species (ROS) Production, Mitochondrial Membrane Potential Loss and Suppression of Mitogen-Activated Protein Kinase (MAPK) and PI3K/AKT Signaling Pathways. (Pubmed Central) - Sep 12, 2019
In MDA-T32 cells, ferruginol might also block the MAPK and PI3K/AKT signaling pathway, which is believed to be an important therapeutic target of anticancer drugs. CONCLUSIONS In conclusion, in view of the results of this study, it might be suggested that ferruginol might serve as an essential lead molecule for the treatment of thyroid cancer provided further in-depth studies especially studying ferruginol toxicological as well as in vivo studies are needed.
- | gemcitabine / generics
Journal, IO Biomarker: Antiproliferative Effects of Matricine in Gemcitabine-Resistant Human Pancreatic Carcinoma Cells Are Mediated via Mitochondrial-Mediated Apoptosis, Inhibition of Cell Migration, Invasion Suppression, and Mammalian Target of Rapamycin (mTOR)-TOR/PI3K/AKT Signalling Pathway. (Pubmed Central) - Sep 12, 2019
We found that matricine efficiently blocked this pathway, suggesting the anticancer potential of matricine. CONCLUSIONS Matricine induced antiproliferative effects in capan-2 human pancreatic cancer cells through inducing apoptosis, caspase activation, inhibition of cell migration and invasion, and blocking the mTOR/PI3K/AKT signalling pathway.
- | Journal: SIRT4 suppresses the PI3K/Akt/NF‑κB signaling pathway and attenuates HUVEC injury induced by oxLDL. (Pubmed Central) - Sep 12, 2019
Furthermore, SIRT4 overexpression suppressed the PI3K/Akt/NF‑κB pathway by inhibiting PI3K phosphorylation and phosphorylated (p)‑Akt, p‑nuclear factor of kappa light polypeptide gene enhancer in B‑cells inhibitor α and p‑p65 NF‑κB expression; blocking p65 NF‑κB nuclear translocation and decreasing interleukin (IL)‑1β, IL‑6, and tumor necrosis factor α expression in oxLDL‑induced HUVECs. In conclusion, SIRT4 overexpression enhanced HUVEC survival, suppressed the PI3K/Akt/NF‑κB signaling pathway and inhibited the expression of inflammatory cytokines in oxLDL‑induced HUVECs.
- Erbitux (cetuximab) / Eli Lilly, EMD Serono, buparlisib (BKM120) / Novartis, Adlai Nortye
Buparlisib (BKM120) in refractory head and neck squamous cell carcinoma harbouring or not a PI3KCA mutation: A phase II multicenter trial (Bilbao Auditorium (Hall 5)) - Sep 11, 2019 - Abstract #ESMO2019ESMO_3256;
P2
Clinical trial identification: NCT01737450. Legal entity responsible for the study: Centre Léon Bérard.
- linsitinib (ASP7487) / Astellas, dactolisib (RTB101) / Novartis, PureTech, xentuzumab (BI-836845) / Boehringer Ingelheim, Eli Lilly
Preclinical evaluation targeting both IGF1R and IR in triple negative breast cancer (Poster Area (Hall 4)) - Sep 11, 2019 - Abstract #ESMO2019ESMO_2693;
Legal entity responsible for the study: The authors. Funding: Boehringer Ingleheim.
- MEN1611 / Menarini, Herceptin (trastuzumab) / Roche
Characterization of the mechanism of action and efficacy of MEN1611 (PA799), a novel PI3K inhibitor, in breast cancer preclinical models (Poster Area (Hall 4)) - Sep 11, 2019 - Abstract #ESMO2019ESMO_2689;
P1
Clinical trial identification: NCT03767335. Legal entity responsible for the study: Menarini Ricerche S.p.A.
- Avastin (bevacizumab) / Roche
PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors (Poster Area (Hall 4)) - Sep 11, 2019 - Abstract #ESMO2019ESMO_2546;
P3
In patients treated with these drugs, reduced activity or expression of PIK3R5 may lead to a reduction in NO production, resulting in vasoconstriction and hypertension. This study, for the first time, provides evidence for new predictive genetic markers of drug-induced hypertension that should be further evaluated for other VEGF-pathway inhibitors.