everolimus

Fourteen different articles showed that the use of cytokines and cancer vaccines revealed new possibilities to treat breast cancer with antibodies against PD-1/PD-L1 (pembrolizumab), PI3K/Akt/mTOR (alpelisib and everolimus), CAR T-cell (chimeric antigen receptor), PARP (poly ADP-ribose polymerase), and CTLA4 (cytotoxic T-lymphocyte-associated protein 4), and with representative relevance of changing in tumor microenvironment. Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) targets show also a high effectivity. In recent years, the release of new strategies has become promising, for changing the microenvironment and de-escalation of therapy based on tumor biology, novel biomarkers, and tumor spread.

Endocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

However, whilst targeting EGFR with cetuximab has been approved for the treatment of OSCC, other single-agent inhibitors of the RTKs have shown modest effects in improving survival. In summary, PTPN11 is a promising therapeutic target in OSCC that can be selectively targeted by SHP2 inhibitor such as TNO155. Our findings on the use of mTOR inhibitor, everolimus to overcome resistance to TNO155 are essential to inform on next phases of clinical trials which is warranted for the treatment of OSCC.

The phase 3 clinical trial LITESPARK-005-belzutifan (HIF-2α inhibitor) demonstrated improvement in progression-free survival compared with everolimus in heavily pretreated patients unselected for somatic/germline VHL alterations (an objective response rate of 23% and a median time on therapy of 7.6 months in the belzutifan cohort), resulting in U.S. FDA approval for patients with advanced RCC. Both patients had an excellent clinical response (partial remissions ongoing at >12 and >20 months). Future studies should assess the merits of biomarker selection for belzutifan treatment.

In present study, we find that hypoxia promoted the methylation degree of CBR4 promoter region thus downgraded the expression of CBR4, which promoted GEP-NETs progression and increased the sensitivity of GEP-NETs cells to everolimus. Further, CBR4 interacted with fatty acid synthase (FASN), displaying a down-regulation of FASN by activating the ubiquitin proteasome pathway and suppressed mTOR signaling. Overall, our results uncovers the CBR4/FASN/mTOR axis as a mechanism for tumor development and inspires us a new molecular guide for the therapeutic strategies for GEP-NETs treatment.

These findings support current guidelines and advocate for the inclusion of everolimus in treatment plans for patients with metastatic HR+/HER2- breast cancer, particularly in late-line treatment, with careful consideration of the benefit-risk profile for each patient.

P1/2, N=23, Active, not recruiting, University of Pennsylvania | Trial primary completion date: Oct 2024 --> May 2024

P1/2, N=380, Not yet recruiting, Shanghai Runshi Pharmaceutical Technology Co., Ltd

P3, N=460, Not yet recruiting, Jiangsu Simcere Pharmaceutical Co., Ltd.

For optimal mRCC treatment selection, clinicians must carefully balance efficacy, toxicity, and patient preferences, especially when transitioning between first- and second-line therapies, to provide individualized care.

We selected 108 CLL patient samples with genetic annotation and exposed them ex-vivo to small-molecule inhibitors used clinically (ibrutinib/BTKi, duvelisib/PI3Ki, trametinib/MEKi, everolimus/mTORi, selinexor/XPO1i) or targeting key signaling pathways (compound 26/TLRi, MK2206/AKTi, nutlin-3a/MDM2i, IBET872/BETi) for 48h. In conclusion, the addition of targeted pathway perturbations to the GEP of primary CLL samples can greatly enhance the potential for molecular and functional classification of disease and subgroups. Our study provides a blueprint to use perturbed omics profiling and interaction testing to link disease drivers to pathway activation and function.

P1, N=20, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Sep 2026

P3, N=1069, Active, not recruiting, Eisai Inc. | Trial completion date: Jul 2024 --> Mar 2026

P2, N=120, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

Overall, this study provides encouraging evidence for the potential of m-TOR inhibitor drugs as promising therapeutic agents for both HCC and HCV, warranting further investigation and optimization for clinical applications.

The patient described herein had a TFE-positive uterine malignant PEComa with lung metastasis and responded well to the mTOR inhibitor, everolimus. Close follow-up in the last 3 years showed remission without recurrence or progression.

P1, N=194, Not yet recruiting, The University of Texas Health Science Center at San Antonio

P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2024 --> Apr 2025

P=N/A, N=30, Completed, University of Kansas Medical Center | Recruiting --> Completed

Sensitivity to paclitaxel and 7-ethyl-10-hydroxycamptothecin, which are substrates for ABCB1 and ABCG2, respectively, was enhanced in Caco/EV, but not in Caco-2 cells. The IC50 values of cisplatin were comparable in both cell lines. Furthermore, mRNA expression levels of ABCB1 and ABCG2 were lower in Caco/EV cells than in Caco-2 cells, and the cellular accumulation of Rhodamine 123 was significantly higher in Caco/EV cells. These findings demonstrated that continuous exposure to everolimus suppressed the expression and function of ABCB1 and ABCG2, suggesting potential drug-drug interactions via the suppression of ABCB1 and ABCG2 in the intestinal tract.

P1, N=1200, Recruiting, Amgen | Trial completion date: Jun 2029 --> Mar 2028 | Trial primary completion date: Jan 2027 --> Apr 2026

P3, N=320, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2024 --> Mar 2026

P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Jun 2029 | Trial primary completion date: Sep 2025 --> Jan 2027

Specifically, this paper focuses on thesubcategories of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) thatexpress somatostatin receptors and are considered suitable for RLT, according to internationalguidelines.

Neurological manifestations can include subependymal giant cell astrocytomas (SEGAs), high rates of infantile spasms, drug-resistant epilepsy, developmental delay, cognitive impairment, autism spectrum disorder, and other neurobehavioral manifestations. Here we review the potential clinical manifestations of TSC by system, recommended diagnostic and surveillance testing, genetic testing, currently available therapeutic options, and considerations for education and social support resources given the unique challenges of this multi-system disorder.

Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) and everolimus (EVE) are effective for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC)...The 5y OS of patients in Group A or Group B were 62.0 % vs 57.4 %, P = 0.569. We found that no matter CDK4/6i or EVE was used first, the survival were not significantly different between Group A and Group B. Both can be clinical options.

The last treatments received prior to the NEC-like transformation included PRRT (n = 3), somatostatin analog, everolimus, sunitinib (n = 1 each), and alkylating agents (n = 2). These findings are most likely attributable to the novel TP53 mutation, which was detected in all nine cases at the last evaluation. However, none of the cases exhibited a complete transformation to a typical NEC, as the tumors retained partial histological and genetic features of NETs.

P2, N=65, Completed, University of California, San Francisco | Active, not recruiting --> Completed

P1/2, N=24, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | N=10 --> 24

P2, N=120, Not yet recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Jan 2027 --> May 2027

P1/2, N=32, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | N=14 --> 32

P2, N=620, Recruiting, Fudan University | N=140 --> 620

P1, N=155, Recruiting, Olema Pharmaceuticals, Inc. | N=90 --> 155 | Trial completion date: Aug 2024 --> Jun 2026 | Trial primary completion date: Aug 2024 --> May 2026

P2, N=90, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P=N/A, N=682, Completed, Institut Curie | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Sep 2024

Even though several therapeutic options are available for the treatment of TSC, there is further need for a better understanding of the pathophysiological basis of the neurologic and other manifestations seen in TSC, and for novel therapeutic approaches. This review provides an overview of the main current therapies for TSC and discusses recent studies highlighting the repurposing of approved drugs and the emerging role of novel targets for future drug design.

Since the tumor harbored a tumor mutational burden of 23/Mb and a programmed death-ligand 1 tumor positivity score of 50%, the patient was treated with pembrolizumab as a second line of systemic therapy, in combination with everolimus. The use of checkpoint inhibitors may be a relevant therapeutic strategy in these patients. It is also the first report on selective internal radiation therapy in PEComas.

In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases.

P2, N=100, Recruiting, Nationwide Children's Hospital | Not yet recruiting --> Recruiting

The in-silico analysis indicated that the significant increase in KDR expression during the initiation of KIRC could serve as an early diagnostic marker. Moreover, KDR could be utilized to identify advancements in KIRC stages. Additionally, hsa-miR-200c-3p was identified as a potential regulator capable of downregulating and upregulating KDR expression among the 24 miRNAs screened. This find-ing holds promise for future research endeavors. Concurrent administration of the FDA-approved 5-fluor-ouracil with KIRC drugs, such as sorafenib, zidovudine, and everolimus, may have the potential to en-hance the therapeutic efficacy in downregulating hsa-miR-200c-3p. However, further in vitro studies are imperative to validate these findings and gain a comprehensive understanding of the intricate regulatory interplay involving hsa-miR-200c-3p, KDR, 5-fluorouracil, and other FDA-approved drugs for the treat-ment of KIRC. This will facilitate the identification of KIRC stage progression and its underlying pre-ventative mechanisms.

P2, N=74, Completed, GOG Foundation | Active, not recruiting --> Completed

P2, N=343, Completed, Eisai Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2024 --> Jun 2024