New drugs from the sea.
This paper illustrates some biochemical and pharmacological properties of two natural marine products such as trabectedin (ET-743, Yondelis) and aplidine. Trabectedin has shown clinical antitumor activity in refractory soft tissue sarcoma and ovarian cancer. The lack of cross resistance of trabectedin with other chemotherapeutic drugs is presumably related to its peculiar mode of action, that seems to be related to a promoter-dependent transcription modulation. Aplidine is a potent pro-apoptotic inducer in human leukemia and has antiangiogenic properties. These examples support the view that more research should be carried out to investigate new natural marine products since there are compounds among them with antitumor properties. Some of them appear to act by mechanisms different from those of conventional chemotherapeutic drugs and thus may be effective against tumors for which no active drugs are available.
D'Incalci
M
M
Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri", Via Eritrea 62, Milan, Italy. dincalci@marionegri.it
Simone
M
M
Tavecchio
M
M
Damia
G
G
Garbi
A
A
Erba
E
E
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D047630:Depsipeptides / Q000737:chemistry / Q000494:pharmacology*; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008386:Marine Biology; D010456:Peptides, Cyclic; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D047630:Depsipeptides; D004149:Dioxoles; D007546:Isoquinolines; D010456:Peptides, Cyclic; D004364:Pharmaceutical Preparations; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; C098980:plitidepsin