Mechanistically, AIM2 promoted FOXO3a phosphorylation and proteasome degradation, thereby reducing its transcriptional effect on ACSL4 and inhibiting ferroptosis. In summary, AIM2 promoted RCC progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis, which could provide new ideas and therapeutic targets for RCC diagnosis and treatment.

TPX2 was a prognostic and therapeutic biomarker in PRCC2. Higher abundance of tumor infiltrating M1 macrophage was significantly associated with worse overall survival in PRCC2. mTOR inhibitors may have good efficacy in patients with high-risk PRCC2.

Low risk patients were more sensitive to small molecule drugs including Erlotinib, Sunitinib, MG-132, CGP-082996, AZ628, Sorafenib, VX-680, and Z-LLNle-CHO. Four risk genes (CALB1, CPA3, NOXA1, and TNNT1) had significant positive correlation with their methylation level, while six genes (CCL22, GPRC5B, HSPA1A, MFNG, PABPC1L, and PCOLCE2) were negatively correlated with their methylation level. This study provides novel understanding of heterogeneity in COAD from the perspective of senescence, and develops signatures for prognosis prediction in COAD.

Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2)...An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.

P2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Mar 2023 --> Mar 2025 | Trial primary completion date: Mar 2023 --> Mar 2025

Through the R package pRRophetic, drug sensitivity tests showed that the low-risk score group would benefit more from sunitinib and less from pazopanib, sorafenib, temsirolimus, gemcitabine and doxorubicin than the high-risk score group. We performed the relevant basic assay validation for CPT1B, and the proliferation ability of RCC cells was inhibited after the knockdown of protein expression of CPT1B. In conclusion, we established a four-gene model that can predict outcomes of RCC with potential applications in diagnosis and treatment.

KIT hotspot mutation (p.A502_Y503dup) has the highest incidence, which may further eliminate the need for whole genome sequencing and patient-specific neoantigen prediction and synthesis. Therefore, for those carrying such mutation, accounting for around 16% of Chinese GIST patients, and are usually less sensitive to imatinib, effective immunotherapies are in prospect.

Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.

P=N/A, N=258, Recruiting, Xiangya Hospital of Central South University

P2, N=46, Recruiting, Fudan University | Not yet recruiting --> Recruiting

Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.

According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.

This review focuses on the signaling pathways and the involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer oncogenic potential downstream of the VHL-HIF-2α signaling axis in ccRCC. Discussed as well are current treatment options (including receptor tyrosine kinase inhibitors such as sunitinib), the medical challenges (high prevalence of metastasis at the time of diagnosis, refractory nature of advanced disease to current treatment options), scientific challenges and future directions.

The most common change was the use of sunitinib and regorafenib in patients with SDH-deficient GIST. The mutation testing rates at primary care centres continue to be low. Despite the hurdles, a large percentage of our patients underwent molecular testing, aiding in therapeutic decision-making.

In the mouse model, Sun suppressed the expression of CD206 and Ki67, simultaneously inhibiting the polarization of JAK1-STAT6 signaling. Sunitinib can suppress the M2 polarization of macrophages to exert the anti-HCC effect, which is its another anticancer mechanism.

Sunitinib and regorafenib are approved in the second- and third-line setting, respectively, with activity against certain secondary mutations with comparatively much lower response rates and survival increment compared to imatinib. Although the efficacy of ripretinib in this unselected patient population was not significantly different from that of sunitinib, the tolerability profile was better. This review article aims to review the efficacy and tolerability profile of ripretinib, together with its role in the setting of unresectable or metastatic GIST.

A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious.

Finally, we demonstrated that LINC02154 and our constructed risk signature could predict outcomes and have potential clinical value.

Compound 6f was the most promising antiproliferative agent against MCF-7 (human breast cancer) with an IC value of 14.77 µM compared to 5-fluorouracil (5FU) (IC = 2.02 µM). Notably, compound 6f hampered receptor tyrosine EGFR fundamentally with an IC value of 1.38 µM, compared to the reference sunitinib with an IC value of 0.08 µM...In silico molecular-docking results of compound 6f in the ATP-binding site of EGFR agreed with the in vitro results. Besides, the investigation of the physicochemical properties of compound 6f via the egg-boiled method clarified good lipophilicity, GIT absorption, and blood-brain barrier penetration properties.

Treatments with BI.2536, Epothilone.B, Gemcitabine, Mitomycin.C, Obatoclax. Mesylate, and Sunitinib may profit high-risk patients...Our data highlight FRGs and CRGs in clinical practice and suggest ferroptosis and cuproptosis may be therapeutic targets for HCC patients. To validate the model's clinical efficacy, more HCC cases and prospective clinical assessments are needed.

Interestingly, the regulatory T cells were significantly decreased by P4, implying the role of peptide in tumor niche. Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and proposed the development of advanced therapeutic approaches against AML by using immune cells.

Finally, NMR results showed that glioblastoma cells treated with hybrid 1, 3 or lapatinib displayed changes in CH /CH signal ratio and choline signals that could indicate necrotic cell death mechanism, meanwhile 2-, sunitinib- or erlotinib-treated cells showed apoptotic characteristic behaviors. Additionally, carboranyl-hybrid 2 also produced autophagy in U87 MG cells.

Imatinib is the mainstay of treatment in patients with recurrent GISTs, and sunitinib may be considered if the patient becomes resistant to imatinib, or surgical treatment may be considered if the lesion can be resected. In this study, we report a case of GIST with peritoneal dissemination in which imatinib therapy was continued after surgery, but the disease recurred twice. We investigate the prognostic value of continued imatinib therapy after surgical resection of locally recurrent GIST.

The efficacy and retinal toxicity profiles of sunitinib suggest that it could potentially be repurposed for local chemotherapy of RB.

P2, N=25, Completed, University Health Network, Toronto | Active, not recruiting --> Completed

In addition, NLRP3 mutation-sensitive drugs (VNLG/124, sunitinib, linifanib) may have better clinical benefits in the high-risk group. All in all, the crLncRNAs model has excellent specificity and sensitivity, which can be used for classifying the therapy-sensitive population and predicting the prognosis of HCC patients.

Compounds 4b, 4d, 5d, and 6b had the most potent antiproliferative activity, with IC values ranging from 2.14 to 19.34 µM, compared to the reference drugs, doxorubicin and sunitinib. Moreover, compound 6b induced caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Finally, a molecular docking simulation was performed for compound 6b to predict the potential ligand-protein interactions with the active sites of the EGFR, HER2, and VEGFR2 proteins.

P1, N=24, Not yet recruiting, National Cancer Institute (NCI)

Imatinib mesylate revolutionized the management of advanced/metastatic GIST, and remains the standard first-line therapy in this setting. Upon development of secondary resistance, sunitinib and regorafenib are used as subsequent treatments, although clinical benefit is often non-durable...Ripretinib is safe and effective therapy for the fourth-line setting in advanced/ metastatic GIST. Future studies should evaluate combination schedules and the identification of markers predictive of benefit from ripretinib.

P2, N=720, Recruiting, Canadian Cancer Trials Group | Trial completion date: Sep 2023 --> Jan 2027 | Trial primary completion date: Jun 2023 --> Jan 2026

Sunitinib resistance (SR) was induced in cell lines by treating sensitive cells with increasing dosages of sunitinib over a 6-month period then maintained by 5 μM suni with each subsequent passage...Interestingly enough, the majority of the differently expressed miRNAs were downwardly expressed showing a return towards a wildtype profile. Further validation of these miRNA to confirm differential expression is ongoing in our lab.

P2, N=90, Active, not recruiting, University Health Network, Toronto | Trial completion date: Oct 2022 --> Dec 2023 | Trial primary completion date: Oct 2022 --> Dec 2023

P2, N=137, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Sep 2022 --> Sep 2023

The biological in vitro analysis confirmed the highest impacts of the targeted MMSNPs in MUC-1 overexpressing cells (OVCAR-3) compared to the MUC-1 negative MDA-MB-231 cells. In conclusion, the synthesized MMSNP-SUN-MUC-1 nanosystem serves as a unique multifunctional targeted delivery system to combat the MUC-1 overexpressing ovarian cancer cells.

Moreover, Immune-E was more sensitive to traditional chemotherapy drugs Cisplatin, Sunitinib, Crizotinib, Dasatinib, Bortezomib, and Midostaurin in both the TCGA and GSE cohorts. Furthermore, a 6-gene signature was constructed to predicting prognosis, which performed better than TIDE score. The performance of IMscore model was successfully validated in three independent datasets and pan-cancer.

Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE-821, Itraconazole, JNJ-42756493, IWR-1, and Linsitinib. In conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.

P2, N=48, Recruiting, University of Miami | Trial completion date: Jan 2028 --> Apr 2028 | Initiation date: Jan 2023 --> Apr 2023 | Trial primary completion date: Jan 2026 --> Apr 2026

P2, N=90, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P2, N=126, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

P2, N=46, Not yet recruiting, Fudan University

P2, N=140, Recruiting, Fudan University | Not yet recruiting --> Recruiting

P2, N=40, Recruiting, Asan Medical Center | Unknown status --> Recruiting | Trial completion date: Aug 2021 --> Nov 2023 | Trial primary completion date: Aug 2021 --> Nov 2023