P2, N=148, Recruiting, Odense University Hospital | Not yet recruiting --> Recruiting

P=N/A, N=410, Recruiting, Cook Research Incorporated | Not yet recruiting --> Recruiting

P1, N=26, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Unknown status --> Completed

After prior ICI exposure, VEGFR-TKIs continue to represent the treatment backbone, while later-line options such as hypoxia-inducible factor-2α (HIF-2α) inhibitors and lenvatinib-everolimus further expand sequencing possibilities. Randomized studies have not shown consistent benefit for routine ICI rechallenge in unselected populations. Overall, advanced ccRCC management requires structured individualization, while validated predictive biomarkers and prospective sequencing data remain important unmet needs.

5-Fluorouracil (5-FU) and its prodrugs are widely used drugs for chemotherapy in various cancers. In conclusion, our study reveals that everolimus sensitizes breast cancer to fluoropyrimidines by destabilizing TYMS through modulation of its O-GlcNAcylation. These findings support a promising combination strategy to improve the therapeutic efficacy of 5-FU and capecitabine in breast cancer.

Mechanistically, LGMN binds to integrin αvβ3 on the macrophage surface and restrains M1 polarization by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1)/signal transducer and activator of transcription 1 (STAT1) pathway...These findings reveal the pivotal role of LGMN in restraining sarcoid granulomatous inflammation through suppression of mTORC1/STAT1-driven M1 macrophage polarization. Therefore, LGMN supplementation may be a promising therapeutic strategy for sarcoidosis.

Herein, through systematic screening of Jianwei Xiaoyan Granule (JWXYG)-derived compounds via molecular docking and surface plasmon resonance (SPR), we identified hederagenin as a potent and novel mechanistic target of rapamycin (mTOR) binder (Kd = 1.30 μM)...Importantly, mTOR knockdown abolished hederagenin-mediated LDHA suppression and compromised its therapeutic efficacy, validating mTOR as an essential target. Our findings demonstrated that hederagenin could inhibit inflammation-cancer transformation in CAG via regulation of glycolysis through the mTOR/HIF-1α pathway, which provided new candidate compounds for regulating the transformation of CAG into cancer.

This PROTAC nanoplatform is engineered by self-assembly of alkylated PROTAC prodrugs with human serum albumin (HSA) while simultaneously encapsulating the mTOR inhibitor rapamycin (RAPA) to inhibit extracellular PROTAC efflux...The efficacy of RAPA in overcoming PROTAC resistance was validated with multiple types of PROTACs, underscoring the generality of this approach. The coassembled nanoplatform integrating the alkylated PROTAC prodrug and RAPA highly efficiently suppressed tumor growth in a mouse model of PROTAC-resistant breast cancer.

We deployed our workflow to study schwannoma development and to test two clinically relevant drugs (rapamycin and brigatinib) head-to-head. Our results uncovered the very early onset of heterogeneity and macrophage recruitment to initiating schwannomas, and the unexpectedly distinct impacts of the two drugs on both, highlighting the value of the pipeline for rapid, innovative future drug-testing.

The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

Everolimus (EVER) and tozasertib (TOZA) encapsulated in NP and targeted with dinutuximab β (DTX-β). DTX-β/EVER-TOZA@PEG-b-PLGA may exert cytotoxic and apoptotic effects in NB. The use of targeted nanocarriers in NB treatment may enhance cytotoxic and apoptotic responses specifically in the tumor region.

In this review, we have evaluated the effects of NET therapies, including somatostatin analogues (SSTAs), molecular targeted therapy (everolimus, sunitinib), Peptide Receptor Radionuclide Therapy (PRRT) and chemotherapy on reproductive and sexual function in patients with NETs. While the effects of PRRT and molecular targeted therapy on fertility are as yet poorly defined, chemotherapy has a proven negative impact on fertility, thus, family and pregnancy planning are strongly recommended before initiation of chemotherapy. Finally, data on the effects of NETs treatment on sexual function are very limited, however neuroendocrine tumour can express Oestrogen Receptors/Progesterone Receptors (ER/PR) or testosterone receptors (TR), thus checking tumour tissue for ER/PR/TR status prior to considering hormonal therapy for sexual dysfunction should be considered but warrants additional studies.