everolimus

To investigate therapeutic options, we utilized patient-derived xenograft (PDX) and tumoroid models established from PDX tumors derived from UDEC patient samples to evaluate everolimus (an mTOR inhibitor) and palbociclib (a CDK4/6 inhibitor), alone and in combination. In a clinical cohort of 29 UDEC patients, higher survivin expression showed a trend toward shorter overall and progression-free survival, supporting its role as a prognostic biomarker. These findings highlight dual PI3K/AKT/mTOR and CDK4/6 inhibition as a promising strategy for UDEC and demonstrate the translational value of PDX and tumoroid models in aggressive gynecologic cancers.

P2, N=340, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jun 2029 --> Jun 2030 | Trial primary completion date: Jun 2027 --> Jun 2028

This study aims to address whether simultaneously targeting CTH and mTOR could enhance therapeutic outcomes beyond those achieved by mTOR inhibition alone.CCOC lines were engineered with CTH knockout (KO) or treated with the CTH inhibitor Aviglycine hydrochloride (AVG; ABG-3168); mTOR was blocked with everolimus, a clinical stage mTOR inhibitor...In CTH-deficient models, the synergy was maintained; however, pharmacological inhibition of CTH with AVG did not produce additional effects, indicating dependence on CTH activity and supporting an on-target mechanism. Similar antiproliferative effects with combined treatment were observed in a CTH-expressing Ewing sarcoma (EwS) model.Together, these findings support biomarker-guided strategies and rational combination therapies that achieve dual targeting of mTOR and CTH, thereby disrupting protein translation and hypoxia adaptation in CCOC and other CTH-expressing cancers.

P1, N=48, Not yet recruiting, Instytut Pomnik Centrum Zdrowia Dziecka

BIOMEDE was a randomized phase 2 trial comparing the efficacy in terms of overall survival (OS) (primary endpoint) of epidermal growth factor receptor (EGFR) inhibitor erlotinib, mTOR inhibitor everolimus and multitargeted tyrosine kinase inhibitor dasatinib in combination with radiotherapy in patients with a biopsy-proven DIPG...A cohort of 66 children with the same inclusion criteria and treated previously with temozolomide-based regimen was used to compare outcome...With comprehensive tumor profiling, BIOMEDE validated prognostic biomarkers as well as informative theranostic biomarkers for future trials. ClinicalTrials.gov: NCT02233049 .

After everolimus failure, he received 177Lu-DOTATATE (Lutathera®). Stable disease was maintained for 12 months without severe adverse events, preserving quality of life. 177Lu-PRRT is a promising therapeutic option for high-grade, somatostatin receptor-positive renal NET when other treatments fail.

This case highlights everolimus-associated hypertriglyceridemia in a lung transplant recipient and underscores the need for tight lipid monitoring and early immunosuppression adjustment when severe dyslipidemia emerges.

Nivolumab was initiated after disease progression on everolimus, resulting in durable disease control for over 3 years. Immunohistochemistry revealed high PD-L1 expression and CD8+ T-cell infiltration within the primary tumor. Immune checkpoint inhibitors may be effective treatment options for malignant epithelioid angiomyolipoma with PD-L1 expression and CD8+ T-cell infiltration.

P2, N=70, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2033 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

P2, N=47, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

Furthermore, combining GSK126 with everolimus, an mTOR inhibitor used clinically for pNENs, more effectively inhibited cell proliferation and tumor growth. In summary, Our findings reveal that the EZH2 inhibitor GSK126 induces ferroptosis by inhibiting the PI3K/AKT/mTOR pathway, suppressing pNENs progression, and HMGCS1 may mediate resistance to EZH2 inhibitors, offering new insights into pNENs treatment.

Furthermore, we identify a synergistic antitumor effect between KPT-330 and translation inhibitors, including everolimus and homoharringtonine. Notably, the disruptive impact of KPT-330 on CRC homeostasis extends to other cancer cell lineages, underscoring its broad mechanistic relevance. Collectively, our findings elucidate a novel mechanism through which KPT-330 destabilizes CRC via translational dysregulation and highlight its potential therapeutic utility in combination regimens for DDLPS.