Trabectedin is a novel chemotherapy agent for diffuse large B cell lymphoma

Spriano, Filippo; Chung, Elaine Y.; Panini, Nicolò; Cascione, Luciano; Rinaldi, Andrea; Erba, Eugenio; Stathis, Anastasios; D’Incalci, Maurizio; Bertoni, Francesco; Gatta, Raffaella

doi:10.1111/bjh.15212

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…Trabectedin (ET-743, Yondelis) is a marine alkaloid isolated from the tunicate Ecteinascidia [141]. Approved in Europe as second-line therapy for soft tissue sarcoma, ovarian cancer, leiomyosarcoma and liposarcoma [141], trabectedin is under evaluation in hematological malignancies [170,171,172]. Trabectedin affects tumor cells as well as the TME, given that selective monocyte and TAM targeting and reduction are key components of its anticancer activity [141] (Figure 3D).…”

Section: Targeting the Tme To Counteract Its Tumor-protective Effementioning

confidence: 99%

Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

Aldinucci

Borghese

Casagrande

2019

IJMS

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Classic Hodgkin lymphoma (cHL) is characterized by a few tumor cells surrounded by a protective, immunosuppressive tumor microenvironment composed of normal cells that are an active part of the disease. Hodgkin and Reed–Sternberg (HRS) cells evade the immune system through a variety of different mechanisms. They evade antitumor effector T cells and natural killer cells and promote T cell exhaustion. Using cytokines and extracellular vesicles, they recruit normal cells, induce their proliferation and “educate” (i.e. reprogram) them to become immunosuppressive and protumorigenic. Therefore, alternative treatment strategies are being developed to target not only tumor cells but also the tumor microenvironment. Here we summarize current knowledge on the ability of HRS cells to build their microenvironment and to educate normal cells to become immunosuppressive. We also describe therapeutic strategies to counteract formation of the tumor microenvironment and related processes leading to T cell exhaustion and repolarization of immunosuppressive tumor-associated macrophages.

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Section: Targeting the Tme To Counteract Its Tumor-protective Effementioning

confidence: 99%

Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

Aldinucci

Borghese

Casagrande

2019

IJMS

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“…These molecules activate NK cells; TRB triggers direct and NK-mediated cytotoxicity in multiple myeloma [ 99 ], and both TRB and LUR exert a cytotoxic effect targeting B cells in Chronic Lymphocytic Leukaemia (CLL) [ 43 , 100 ]. TRB exhibited cytotoxic effects in diffuse large B cell leukaemia [ 101 ]. TRB and LUR have been shown to activate CD4 + and CD8 + T-cells as well, promoting the adaptive anti-tumour immune response, inducing their infiltration in vivo and the proliferation of activated effector T-cells in vitro [ 43 , 100 , 102 , 103 ].…”

Section: Mechanism Of Action Of Trabectedin and Lurbinectedinmentioning

confidence: 99%

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

Povo-Retana,

Landauro-Vera,

Alvarez-Lucena

et al. 2024

Molecules

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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.

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“…This was solved by exploiting a semisynthetic method from the microbial product cyanosafracin B, an antibiotic obtained by fermentation of the bacterium Pseudomonas fluorescens [167]. The anticancer activity of trabectedin is supported by data obtained in different tumor models, and its mechanism of action also involved an effect on the tumor microenvironment, mainly on macrophages [3,[168][169][170][171][172][173][174][175][176][177][178]. Since 2007, trabectedin is approved by the EMEA for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide or for those who are unsuited to receive it.…”

Section: Alkaloidsmentioning

confidence: 99%

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

et al. 2020

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The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.

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Trabectedin is a novel chemotherapy agent for diffuse large B cell lymphoma

Cited by 6 publications

References 9 publications

Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

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

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

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