bims-myxlip 2024-01-28 papers

Issue of 2024–01–28
three papers selected by
Laura Mannarino, Humanitas Research

Surg Pathol Clin. 2024 Mar;pii: S1875-9181(23)00068-5. [Epub ahead of print]17(1): 25-29

Myxoid pleomorphic liposarcoma (MPLPS) shows a strong predilection for the mediastinum and can affect a wide age range. Clinically, MPLPS exhibits aggressive behavior and demonstrates a worse overall and progression-free survival than myxoid/round cell liposarcoma (MRLPS) and pleomorphic liposarcoma (PLPS). Histologically, MPLPS is characterized by hybrid morphologic features of MRLPS and PLPS, including myxoid stroma, chicken wire-like vasculature, univacuolated and multivacuolated lipoblasts, and high-grade pleomorphic sarcomatous components. In terms of molecular features, MPLPS is distinct from other lipomatous tumors as it harbors genome-wide loss of heterozygosity.

Keywords: Loss of heterozygosity; Myxoid pleomorphic liposarcoma; TP53

DOI: https://doi.org/10.1016/j.path.2023.06.005

Molecules. 2024 Jan 09. pii: 331. [Epub ahead of print]29(2):

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.

Adrián Povo-Retana, Rodrigo Landauro-Vera, Carlota Alvarez-Lucena, Marta Cascante, Lisardo Boscá.

Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-β-carboline in LUR. TRB is indicated for patients with relapsed ovarian cancer in combination with pegylated liposomal doxorubicin, as well as for advanced soft tissue sarcoma in adults in monotherapy. LUR was approved by the FDA in 2020 to treat metastatic small cell lung cancer. Herein, we systematically summarise the origin and structure of TRB and LUR, as well as the molecular mechanisms that they trigger to induce cell death in tumoral cells and supporting stroma cells of the tumoral microenvironment, and how these compounds regulate immune cell function and fate. Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.

Keywords: adaptative immunity; combined therapies; ecteinascidins; innate immunity; lurbinectedin; lymphocytes; macrophages; molecular oncology; trabectedin

DOI: https://doi.org/10.3390/molecules29020331

Cancers (Basel). 2024 Jan 08. pii: 271. [Epub ahead of print]16(2):

Genetic, Epigenetic and Transcriptome Alterations in Liposarcoma for Target Therapy Selection.

Ekaterina A Lesovaya, Timur I Fetisov, Beniamin Yu Bokhyan, Varvara P Maksimova, Evgeny P Kulikov, Gennady A Belitsky, Kirill I Kirsanov, Marianna G Yakubovskaya.

Liposarcoma (LPS) is one of the most common adult soft-tissue sarcomas (STS), characterized by a high diversity of histopathological features as well as to a lesser extent by a spectrum of molecular abnormalities. Current targeted therapies for STS do not include a wide range of drugs and surgical resection is the mainstay of treatment for localized disease in all subtypes, while many LPS patients initially present with or ultimately progress to advanced disease that is either unresectable, metastatic or both. The understanding of the molecular characteristics of liposarcoma subtypes is becoming an important option for the detection of new potential targets and development novel, biology-driven therapies for this disease. Innovative therapies have been introduced and they are currently part of preclinical and clinical studies. In this review, we provide an analysis of the molecular genetics of liposarcoma followed by a discussion of the specific epigenetic changes in these malignancies. Then, we summarize the peculiarities of the key signaling cascades involved in the pathogenesis of the disease and possible novel therapeutic approaches based on a better understanding of subtype-specific disease biology. Although heterogeneity in liposarcoma genetics and phenotype as well as the associated development of resistance to therapy make difficult the introduction of novel therapeutic targets into the clinic, recently a number of targeted therapy drugs were proposed for LPS treatment. The most promising results were shown for CDK4/6 and MDM2 inhibitors as well as for the multi-kinase inhibitors anlotinib and sunitinib.

Keywords: dedifferentiated liposarcoma; epigenetic changes; liposarcoma; molecular genetic abnormalities; myxoid pleomorphic liposarcoma; myxoid/round-cell liposarcoma; pleomorphic liposarcoma; targeted therapy; well-differentiated liposarcoma

DOI: https://doi.org/10.3390/cancers16020271