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Thyroid : Official Journal of the... Oct 2023Anaplastic thyroid cancer (ATC) is uniformly lethal. mutation is present in 45% of patients with ATC. Targeted therapy with combined BRAF and MEK inhibition in -mutant...
Anaplastic thyroid cancer (ATC) is uniformly lethal. mutation is present in 45% of patients with ATC. Targeted therapy with combined BRAF and MEK inhibition in -mutant ATC can be effective, but acquired resistance is common because this combination targets the same pathway. Drug matrix screening, in ATC cells, of highly active compounds in combination with BRAF inhibition showed multitargeting tyrosine kinase inhibitors (MTKIs) had the highest synergistic/additive activity. Thus, we hypothesized that the combination of inhibition and an MTKI is more effective than a single drug or combined BRAF and MEK inhibition in -mutant ATC. We evaluated the effect of inhibitors in combination with the MTKI axitinib and its mechanism(s) of action. We evaluated the effects of inhibitors and axitinib alone and in combination in and models of -mutant and wild-type ATC. The combination of axitinib and inhibitors (dabrafenib and PLX4720) showed an additive effect on inhibiting cell proliferation based on the Chou-Talalay algorithm in -mutant ATC cell lines. This combination also significantly inhibited cell invasion and migration ( < 0.001) compared with the control. Dabrafenib and PLX4720 arrested ATC cells in the G0/G1 phase. Axitinib arrested ATC cells in the G2/M phase by decreasing phosphorylation of aurora kinase B (Thr232) and histone H3 (Ser10) proteins and by upregulating the c-JUN signaling pathway. The combination of BRAF inhibition and axitinib significantly inhibited tumor growth and was associated with improved survival in an orthotopic ATC model. The novel combination of axitinib and inhibition enhanced anticancer activity in and models of -mutant ATC. This combination may have clinical utility in -mutant ATC that is refractory to current standard therapy, namely combined BRAF and MEK inhibition.
Topics: Humans; Thyroid Carcinoma, Anaplastic; Axitinib; Proto-Oncogene Proteins B-raf; Tyrosine Kinase Inhibitors; Thyroid Neoplasms; Protein Kinase Inhibitors; Mitogen-Activated Protein Kinase Kinases; Mutation; Cell Line, Tumor
PubMed: 37675898
DOI: 10.1089/thy.2023.0201 -
ESMO Open Dec 2023In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in...
Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.
BACKGROUND
In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in patients with advanced renal cell carcinoma across all International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor); analyses of overall survival (OS) remain immature. Here, we report post hoc analyses of efficacy from the third interim analysis (data cut-off, April 2020) by the numbers of IMDC risk factors and target tumor sites at baseline.
METHODS
Efficacy endpoints assessed were PFS, objective response, and best overall response per investigator assessment (RECIST v1.1) and OS. Best percentage change and percentage change from baseline in target tumor size over time during the study were also assessed.
RESULTS
In patients with 0, 1, 2, 3, or 4-6 IMDC risk factors, hazard ratios [HRs; 95% confidence interval (CIs)] for OS with avelumab + axitinib versus sunitinib were 0.660 (0.356-1.223), 0.745 (0.524-1.059), 0.973 (0.668-1.417), 0.718 (0.414-1.248), and 0.443 (0.237-0.829), and HRs (95% CIs) for PFS were 0.706 (0.490-1.016), 0.709 (0.540-0.933), 0.711 (0.527-0.960), 0.501 (0.293-0.854), and 0.395 (0.214-0.727), respectively. In patients with 1, 2, 3, or ≥4 target tumor sites, HRs (95% CIs) for OS with avelumab + axitinib versus sunitinib were 0.912 (0.640-1.299), 0.715 (0.507-1.006), 0.679 (0.442-1.044), and 0.747 (0.346-1.615), and HRs (95% CIs) for PFS were 0.706 (0.548-0.911), 0.552 (0.422-0.723), 0.856 (0.589-1.244), and 0.662 (0.329-1.332), respectively. Across all subgroups, analyses of objective response rate and complete response rate favored avelumab + axitinib versus sunitinib, and a greater proportion of patients treated with avelumab + axitinib had tumor shrinkage.
CONCLUSIONS
In post hoc analyses, first-line treatment with avelumab + axitinib was generally associated with efficacy benefits versus treatment with sunitinib in patients with advanced renal cell carcinoma across subgroups defined by different numbers of IMDC risk factors or target tumor sites.
Topics: Humans; Carcinoma, Renal Cell; Axitinib; Sunitinib; Antineoplastic Agents; Follow-Up Studies; Kidney Neoplasms; Risk Factors
PubMed: 37866029
DOI: 10.1016/j.esmoop.2023.102034 -
Cancer Jan 2021There are limited treatment options for unresectable recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Vascular endothelial growth factor is...
BACKGROUND
There are limited treatment options for unresectable recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Vascular endothelial growth factor is of significant interest for targeted therapy in R/M HNSCC because of its central role in tumorigenesis and immunosuppression. Axitinib is a potent inhibitor of vascular endothelial growth factor receptor (VEGFR) 1 , VEGFR2, VEGFR3, platelet-derived growth factor receptor, as well as c-kit and offers such an approach.
METHODS
This article reports the results of a phase 2 trial evaluating axitinib in R/M HNSCC according to the Choi criteria for radiographic response assessment. The primary endpoint of this trial was 6-month overall survival.
RESULTS
Twenty-nine patients were enrolled, and 28 were evaluable for a response. Patients were heavily pretreated with 61% having had at least 1 previous systemic treatment in the metastatic setting (range, 0-5). The median overall survival of 9.8 months and the 6-month overall survival rate of 70% met the protocol-defined criteria for clinical efficacy. The best overall response rate was 42%. Correlative analyses demonstrated that PI3K signaling pathway alterations were associated with an increased response to therapy (75% vs 17%). A marked response to therapy was seen in a subgroup of patients who were treated with an immune checkpoint inhibitor after progression on axitinib.
CONCLUSIONS
Treatment with axitinib is associated with improved survival in patients with heavily pretreated head and neck cancer, and PI3K pathway alterations may serve as a biomarker for response. Further investigation is warranted to evaluate axitinib in biomarker-selected populations, especially in combination with immune checkpoint inhibitor therapy.
LAY SUMMARY
Metastatic head and neck squamous cancer is an incurable disease with limited treatment options and a poor prognosis. This study is the first to demonstrate that the targeted oral drug axitinib improves survival in patients with heavily pretreated metastatic head and neck cancer. Furthermore, patients whose tumors have specific mutations derive the greatest benefit from therapy. The investigation of axitinib alone or in combination with immunotherapy in a genomic biomarker-selected population is warranted.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Axitinib; Biomarkers, Tumor; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33079405
DOI: 10.1002/cncr.33226 -
British Journal of Cancer Oct 2022Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical...
BACKGROUND
Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor.
METHODS
NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity.
RESULTS
In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype.
CONCLUSIONS
NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery.
CLINICAL TRIAL REGISTRATION
NCT03494816.
Topics: Axitinib; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Neoadjuvant Therapy; Nephrectomy; Retrospective Studies; Thrombosis
PubMed: 35739300
DOI: 10.1038/s41416-022-01883-7 -
BMC Urology Jun 2020Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent...
BACKGROUND
Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent developments in the therapeutic approach include antiangiogenic targeted approaches and Immunotherapy. Thus, the therapeutic algorithm of RCC patients and the survival outcomes have changed dramatically.
METHODS
Herein we present a retrospective study of the patients treated in our Department with an antiangiogenic agent -Axitinib, a tyrosine kinase inhibitor- as a third or further line treatment. Statistical analysis was performed with SPSS, including the available clinicopathological data of the patients included.
RESULTS
Axitinib was found to be active in patients who received this treatment beyond second line. The toxicity profile of this regimen did not reveal any unknown adverse events.
CONCLUSIONS
Our real world data reflect that axitinib is a safe and effective option, even beyond the second line.
Topics: Adult; Aged; Axitinib; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 32487200
DOI: 10.1186/s12894-020-00618-1 -
Head & Neck Dec 2023This study analyzed the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid...
BACKGROUND
This study analyzed the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib.
METHODS
Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole-side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer.
RESULTS
Twenty-seven patients were included in the analysis. The best response was stable disease, and the median progression-free survival (PFS) was 11.1 months (95% CI, 9.2-13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm (IQR, 8.3-73.0) and 180.4/mm (IQR, 69.6-342.8), respectively. Patients with stromal TIL density >342.5/mm exhibited longer PFS (p = 0.012).
CONCLUSIONS
Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment.
Topics: Humans; Artificial Intelligence; Axitinib; Biomarkers; Carcinoma, Adenoid Cystic; Lymphocytes, Tumor-Infiltrating; Neoplasm Recurrence, Local; Prospective Studies
PubMed: 37828867
DOI: 10.1002/hed.27537 -
The Cochrane Database of Systematic... May 2023Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL).
OBJECTIVES
To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable.
DATA COLLECTION AND ANALYSIS
All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm.
MAIN RESULTS
We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being 'high' or 'some concerns' across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB.
AUTHORS' CONCLUSIONS
Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.
Topics: Male; Female; Adult; Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Network Meta-Analysis; Sunitinib
PubMed: 37146227
DOI: 10.1002/14651858.CD013798.pub2 -
In Vivo (Athens, Greece) 2020Whether molecular-targeted therapy, particularly axitinib, is effective after failure of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) remains...
BACKGROUND/AIM
Whether molecular-targeted therapy, particularly axitinib, is effective after failure of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) remains unclear. Here, we evaluated the therapeutic effect of axitinib as a third-line therapy following second-line nivolumab monotherapy for mRCC.
PATIENTS AND METHODS
Data from patients treated with axitinib as a third-line therapy after failure of first-line tyrosine kinase inhibitor (TKI) and second-line nivolumab monotherapy were reviewed. The progression-free survival (PFS), overall survival (OS), and objective response rate during axitinib therapy were retrospectively evaluated. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1.
RESULTS
Seventeen patients were treated with third-line axitinib after failure of prior TKI and nivolumab. During a median follow-up of 8.15 months, eight (47.1%) and three (17.6%) patients showed disease progression and died, respectively. The median PFS was 12.8 months [95% confidence interval=(CI)4.08-21.7], the 1-year PFS rate was 51.3%, and the 1-year OS rate was 71.6%. The median magnitude of maximum changes of targeted lesions from baseline was -11.9% (95%CI=-36.1-0.44%). The objective response rate and disease control rates were 29.4% (n=5) and 94.1% (n=16), respectively. Univariate analysis for PFS showed a shorter PFS in patients with non-clear cell histopathological types or those with liver metastases (p-Value<0.0001 for both).
CONCLUSION
Axitinib as a third-line therapy showed reasonable therapeutic efficacy after the failure of first-line TKI and second-line nivolumab monotherapy for mRCC. Further studies are needed to confirm our findings.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Agents, Immunological; Axitinib; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Nivolumab; Protein Kinase Inhibitors; Retreatment; Treatment Failure; Treatment Outcome
PubMed: 32354960
DOI: 10.21873/invivo.11943 -
Clinical & Experimental Ophthalmology Dec 2018This study evaluated the effects of topically applied axitinib, a tyrosine kinase inhibitor, in an experimental model of corneal neovascularization (CNV).
BACKGROUND
This study evaluated the effects of topically applied axitinib, a tyrosine kinase inhibitor, in an experimental model of corneal neovascularization (CNV).
METHODS
A total of 48 New Zealand rabbits were used. CNV was induced by placing five silk sutures in the upper cornea of one eye per rabbit. Rabbits were randomized into four groups (12 rabbits each): 0.9% saline (control group), 0.02 mg/mL axitinib, 0.35 mg/mL axitinib and 0.5 mg/mL axitinib groups. All treatments were administered three times daily for 14 days. Photographs were taken using a slit lamp on days 7 and 14. The area of neovascularization was measured in mm , as the percentage of total corneal area and as the percentage of corneal surface covered by sutures (SCS).
RESULTS
On day 14, the CNV area in the control group (31.50 ± 7.47 mm ; 115.00 ± 22.55% of the corneal SCS) was larger than that in the 0.02 mg/mL axitinib group (19.20 ± 8.92 mm ; 73.89 ± 34.98%), the 0.35 mg/mL axitinib group (8.83 ± 3.92 mm ; 31.90 ± 13.59%) and the 0.5 mg/mL axitinib group (5.12 ± 3.97 mm ; 18.38 ± 13.65%). Compared with saline, CNV was inhibited 39.04% by 0.02 mg/mL axitinib, 71.96% by 0.35 mg/mL axitinib and 84.73% by 0.5 mg/mL axitinib.
CONCLUSION
Topical administration of the three axitinib concentrations inhibited CNV in rabbits, blocking both vascular endothelial growth factor and platelet-derived growth factor pathways. Axitinib at 0.5 mg/mL induced profound inhibition of corneal angiogenesis.
Topics: Animals; Rabbits; Administration, Topical; Axitinib; Cornea; Corneal Neovascularization; Disease Models, Animal; Dose-Response Relationship, Drug; Follow-Up Studies; Microvessels; Ophthalmic Solutions; Protein Kinase Inhibitors; Random Allocation; Treatment Outcome
PubMed: 29888852
DOI: 10.1111/ceo.13333 -
Proceedings of the National Academy of... Aug 2016Oncogenic mutations of the Wnt (wingless)/β-catenin pathway are frequently observed in major cancer types. Thus far, however, no therapeutic agent targeting...
Oncogenic mutations of the Wnt (wingless)/β-catenin pathway are frequently observed in major cancer types. Thus far, however, no therapeutic agent targeting Wnt/β-catenin signaling is available for clinical use. Here we demonstrate that axitinib, a clinically approved drug, strikingly blocks Wnt/β-catenin signaling in cancer cells, zebrafish, and Apc(min/+) mice. Notably, axitinib dramatically induces Wnt asymmetry and nonrandom DNA segregation in cancer cells by promoting nuclear β-catenin degradation independent of the GSK3β (glycogen synthase kinase3β)/APC (adenomatous polyposis coli) complex. Using a DARTS (drug affinity-responsive target stability) assay coupled to 2D-DIGE (2D difference in gel electrophoresis) and mass spectrometry, we have identified the E3 ubiquitin ligase SHPRH (SNF2, histone-linker, PHD and RING finger domain-containing helicase) as the direct target of axitinib in blocking Wnt/β-catenin signaling. Treatment with axitinib stabilizes SHPRH and thereby increases the ubiquitination and degradation of β-catenin. Our findings suggest a previously unreported mechanism of nuclear β-catenin regulation and indicate that axitinib, a clinically approved drug, would provide therapeutic benefits for cancer patients with aberrant nuclear β-catenin activation.
Topics: Animals; Axitinib; Cell Division; DNA Helicases; Glycogen Synthase Kinase 3 beta; HCT116 Cells; Humans; Imidazoles; Indazoles; Male; Mice; Mice, Inbred C57BL; Neoplasms; Protein Kinase Inhibitors; Regeneration; Ubiquitin-Protein Ligases; Wnt Signaling Pathway; Zebrafish; beta Catenin
PubMed: 27482107
DOI: 10.1073/pnas.1604520113