bims-mesote 2025-01-26 papers

Issue of 2025–01–26
two papers selected by
Laura Mannarino, Humanitas Research

ESMO Open. 2025 Jan 21. pii: S2059-7029(24)01894-5. [Epub ahead of print]10(2): 104123

Follow-up after first-Line nivOlumab plus ipilimumab in patients with diffuse pleuRal mesotheliomA: a real-world Dutch cohort study-FLORA.

L H Douma, M M Hofman, F Zwierenga, T M T Zondervan, A I G Buma, H Schouwink, D W Dumoulin, J A Burgers, I Smesseim, J G J V Aerts, C J de Gooijer.

BACKGROUND: Diffuse pleural mesothelioma (dPM) is an aggressive malignancy, primarily treated with palliative systemic therapy. Since 2022, nivolumab-ipilimumab (nivo/ipi) has replaced chemotherapy as the standard first-line treatment for dPM in the Netherlands. Chemotherapy remains a rational second-line treatment. The real-world effectiveness of second-line treatment after doublet immunotherapy remains unknown. The FLORA study aimed to provide an overview of treatment patterns in patients with dPM after first-line nivo/ipi and evaluate the effectiveness of second-line chemotherapy based on real-world data.
PATIENTS AND METHODS: FLORA was a Dutch multicenter retrospective cohort study. Clinical data were collected from the medical records. The primary endpoints were treatment patterns after nivo/ipi and median overall survival (mOS) of patients receiving second-line chemotherapy. The secondary endpoints were objective response rate (ORR), median progression-free survival (mPFS) of second-line chemotherapy, and subgroup analyses (Eastern Cooperative Oncology Group performance status and histological subtype). The study also updated the mOS for first-line nivo/ipi patients.
RESULTS: Between May 2021 and July 2023, 277 patients with dPM receiving first-line nivo/ipi therapy were included. Sixty-eight percent of the patients were male, with a median age of 72 years (interquartile range 67-77 years). The histological subtypes were epithelioid (62%), sarcomatoid (22%), biphasic (13%), and unknown (3%). One hundred and two (47%) of the 218 patients with disease progression received second-line treatment, of whom 83 received second-line platinum-pemetrexed chemotherapy. The mOS and mPFS for second-line chemotherapy were 8.2 months ([95% confidence interval (CI) 7.4-9.1 months] and 5.6 months (95% CI 4.9-6.3 months), respectively, with an ORR of 37%. Poor performance score was the main reason for not receiving second-line treatment.
CONCLUSION: This study provides the first real-world data on subsequent treatment of patients with dPM with disease progression on nivo/ipi, resulting in an mOS of 8.2 months after second-line chemotherapy.

Keywords: chemotherapy; dual immune checkpoint inhibitors; mesothelioma

DOI: https://doi.org/10.1016/j.esmoop.2024.104123

Mar Drugs. 2025 Jan 10. pii: 32. [Epub ahead of print]23(1):

Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma.

Angélica Luna-Nophal, Fernando Díaz-Castillo, Vanessa Izquierdo-Sánchez, Jesús B Velázquez-Fernández, Mario Orozco-Morales, Luis Lara-Mejía, Johana Bernáldez-Sarabia, Noemí Sánchez-Campos, Oscar Arrieta, José Díaz-Chávez, Jorge-Ismael Castañeda-Sánchez, Alexei-Fedorovish Licea-Navarro, Saé Muñiz-Hernández.

Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules. This study analyzed the anticancer effects in vitro and in vivo of two peptides found in C. californicus. The effects of s-cal14.1b and s-cal14.2b on cell proliferation, apoptosis, and cytotoxicity were evaluated in 2D and 3D cultures of MPM-derived cells. Proteomics analysis of 3D cultures treated with conotoxins was performed to examine changes in expression or abundance. And the therapeutic effects of both conotoxins were evaluated in MPM mouse xenografts. s-cal14.1b and s-cal14.2b induced apoptosis and cytotoxicity in 2D and 3D cultures. However, only s-cal14.1b modified spheroid growth. Approximately 600 proteins exhibited important differential expression, which was more heterogeneous in H2452 vs MSTO-211H spheroids. The in silico protein functional analysis showed modifications in the biological pathways associated with carcinogenesis. CAPN1, LIMA1, ANXA6, HUWE1, PARP1 or PARP4 proteins could be potential cell targets for conotoxins and serve as biomarkers in MPM. Finally, we found that both conotoxins reduced the tumor mass in MPM xenografts; s-cal14.1b reached statistical significance. Based on these results, s-cal14.1b and s-cal14.2b conotoxins could be potential therapeutic drugs for MPM neoplasms with no apparent side effects on normal cells.

Keywords: marine toxins; mass spectrometry; pharmacological activity; protein markers; therapeutic effect

DOI: https://doi.org/10.3390/md23010032