Our results show that parthenolide covalently binds to Cys54 of BUGZ via Michael addition to its α-methylene-γ-lactone moiety. Since Cys54 is located within the second zinc-finger domain of the BUGZ microtubule-targeting region, we propose that parthenolide interferes with the microtubule-binding ability of BUGZ, consequently preventing kinetochore-microtubule attachments required for accurate chromosome congression to the spindle equator.

P1, N=9, Completed, CicloMed LLC | Trial completion date: Dec 2022 --> Apr 2023 | Trial primary completion date: Dec 2022 --> Apr 2023

P1/2, N=18, Terminated, CicloMed LLC | Phase classification: P1b/2a --> P1/2 | N=28 --> 18 | Recruiting --> Terminated; Discontinued

P2, N=12, Completed, CicloMed LLC | Active, not recruiting --> Completed

OBSERVATION: Among available treatments, it is possible to distinguish lesion-directed therapies (cryotherapy, laser therapy, conventional photodynamic theapy and surgery when a progression to iSCC is suspected) and field-directed therapies (5-fluorouracil, diclofenac,piroxicam, imiquimod and daylight photodynamic therapy)associated to daily appropriate photoprotection...We evaluated efficacy, safety and adherence to therapy of topical ointments indicated for the treatment of the different clinico-pathologic variants of AK (focusing on tirbanibulin and 5-Fluorouracil 0.5%, Salicylic Acid 10%), providing a clinical, dermoscopic and OCT longitudinal evaluation...Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis...2021;384(6):512-520. doi:10.1056/NEJMoa2024040

Clinical responses to nivolumab and pembrolizumab, in particular, are promising...In regard with safety profile, adverse events (AEs) related to anti-PD-(L)1 are lower compared with that for platinum-based and docetaxel therapy. Toripalimab is the safest among various immunotherapy drugs...Appropriate biomarker selection will improve therapy outcomes in ICI treated NSCLC patients, particularly in cases under combinatory ICI therapy. Application of bispecific antibodies and EV-based targeted therapy are effective novel strategies to improve therapeutic outcomes in cancer patients.

Only the phase III KEYNOTE-775 trial reported a statistically significant overall survival improvement for the combination of pembrolizumab plus lenvatinib compared with docetaxel or paclitaxel regardless of MMR/MSI status. Pembrolizumab plus lenvatinib is indicated for patients with unselected pretreated metastatic endometrial cancer and pembrolizumab monotherapy is a preferred option for patients with MMRd/MSI-H tumors.

Inactivating mutations in SPOP are associated with better response to ARSI treatment in mCRPC overall. Additional analysis with a larger cohort is needed to evaluate the association of SPOP status and outcomes with docetaxel. Race-associated clinical outcomes and molecular features were observed, suggesting the benefit of biomarker-directed therapy selection for individualized patient subsets in guiding treatment decisions for mCRPC patients.

After comprehensive analysis of different risk groups, the efficacy of the high-risk group on bleomycin, cisplatin, docetaxel, doxorubicin and etoposide was better than that of the low-risk group, suggesting that risk subgroups based on risk scores play a guiding role in chemotherapy and that the high-risk group may benefit more from immunotherapy. RT-qPCR results showed that LINC00924, LINC00944, and LINC00865 were highly expressed in tumour tissues, while LINC00702 and ZFAS1 were expressed at low levels in tumour tissues. In conclusion, we were the first to discover that m7G-related lncRNAs play a vital role in the tumour immune microenvironment of gastric cancer, and a risk prediction model was established to identify patients with potential benefits from immunotherapy and predict the prognosis of GC patients.

Conversely, the secretion of interferon-γ and tumor necrosis factor-α were increased. Our study provided a promising therapeutic strategy for HNSCC.

Although only a minority of MBC patients are concerned, taxane rechallenge appears to be a pragmatic option with an acceptable tolerance, and good efficacy, especially when these drugs have shown clinical activity earlier in the disease course, and/or have been stopped for reasons other than progression.

The comparators in the untreated population were pembrolizumab + pemetrexed + chemotherapy and pembrolizumab monotherapy. The comparators for the pre-treated population were docetaxel monotherapy, docetaxel + nintedanib, and platinum-based chemotherapy ± pemetrexed...The uncertainty of the clinical evidence and the estimates of cost effectiveness were too high to be considered a cost-effective use of NHS resources. Therefore, pralsetinib was not recommended for routine use.