bims-myxlip 2023-02-12 papers

Front Oncol. 2023 ;13 1095219

Targeting cyclin-dependent kinases in sarcoma treatment: Current perspectives and future directions.

Alessandra Merlini, Valeria Pavese, Giulia Manessi, Martina Rabino, Francesco Tolomeo, Sandra Aliberti, Lorenzo D'Ambrosio, Giovanni Grignani.

Effective treatment of advanced/metastatic bone and soft tissue sarcomas still represents an unmet medical need. Recent advances in targeted therapies have highlighted the potential of cyclin-dependent kinases (CDK) inhibitors in several cancer types, including sarcomas. CDKs are master regulators of the cell cycle; their dysregulation is listed among the "hallmarks of cancer" and sarcomas are no exception to the rule. In this review, we report both the molecular basis, and the potential therapeutic implications for the use of CDK inhibitors in sarcoma treatment. What is more, we describe and discuss the possibility and biological rationale for combination therapies with conventional treatments, target therapy and immunotherapy, highlighting potential avenues for future research to integrate CDK inhibition in sarcoma treatment.

Keywords: cdk inhibitors; cell cycle; cyclin dependent kinases (CDK); sarcoma; target therapy

DOI: https://doi.org/10.3389/fonc.2023.1095219

Cancers (Basel). 2023 Jan 31. pii: 906. [Epub ahead of print]15(3):

SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced Soft Tissue Sarcoma.

Erlinda Maria Gordon, Sant P Chawla, Walter Andree Tellez, Elan Younesi, Sonu Thomas, Victoria S Chua-Alcala, Hripsime Chomoyan, Chrysler Valencia, Don Arlen Brigham, Ania Moradkhani, Doris Quon, Amornchit Srikureja, Steven G Wong, William Tseng, Noah Federman.

BACKGROUND: This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma.METHODS: Phase I endpoints-maximum tolerated dose in previously treated patients; Phase II endpoints-best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments-escalating doses of trabectedin (1.0, 1.2, 1.5 mg/m2) as continuous intravenous infusion over 24 h every 3 weeks, 1 mg/kg of ipilimumab given intravenously every 12 weeks, and 3 mg/kg of nivolumab given intravenously every 2 weeks; Phase II treatments-maximum tolerated dose of trabectedin and defined doses of ipilimumab and nivolumab.
RESULTS: Phase I (n = 9)-the maximum tolerated dose of trabectedin was 1.2 mg/m2; Phase II (n = 79)-6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median progression-free survival, 6.7 months (CI 95%: 4.4-7.9), median overall survival, 24.6 months (CI 95%: 17.0-.); Grade 3/4 therapy-related adverse events (n = 92)-increased ALT (25%), fatigue (8.7%), increased AST (8.7%), decreased neutrophil count (5.4%) and anemia (4.6%).
CONCLUSION: SAINT is a safe and effective first-line treatment for advanced soft tissue sarcoma.

Keywords: alkylating agent; chemotherapy; immune checkpoint inhibitor; immunotherapy; ipilimumab; nivolumab and trabectedin; soft tissue sarcoma

DOI: https://doi.org/10.3390/cancers15030906

Front Oncol. 2022 ;12 1115342

Editorial: Trabectedin, lurbinectedin, and other marine-derived anticancer alkaloids on solid cancer: Mechanisms of action, clinical impact, and future perspectives.

Alberto Zambelli, Maurizio D'Incalci.

Keywords: eribulin and related compounds; lurbinectedin; marine drugs; solid tumor; trabectedin

DOI: https://doi.org/10.3389/fonc.2022.1115342