Trabectedin and plitidepsin: drugs from the sea that strike the tumor microenvironment.
The prevailing paradigm states that cancer cells acquire multiple genetic mutations in oncogenes or tumor suppressor genes whose respective activation/up-regulation or loss of function serve to impart aberrant properties, such as hyperproliferation or inhibition of cell death. However, a tumor is now considered as an organ-like structure, a complex system composed of multiple cell types (e.g., tumor cells, inflammatory cells, endothelial cells, fibroblasts, etc.) all embedded in an inflammatory stroma. All these components influence each other in a complex and dynamic cross-talk, leading to tumor cell survival and progression. As the microenvironment has such a crucial role in tumor pathophysiology, it represents an attractive target for cancer therapy. In this review, we describe the mechanism of action of trabectedin and plitidepsin as an example of how these specific drugs of marine origin elicit their antitumor activity not only by targeting tumor cells but also the tumor microenvironment.
Cell Biology and Pharmacogenomics Department, PharmaMar, Madrid 28770, Spain. cgalmarini@pharmamar.com.
Carlos M
CM
Galmarini
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan 20156, Italy. maurizio.dincalci@marionegri.it.
Maurizio
M
D'Incalci
Department Immunology and Inflammation, IRCCS Clinical and Research Institute Humanitas, Rozzano, Milan 20089, Italy. paola.allavena@humanitasresearch.it.
Paola
P
Allavena
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D059001:Aquatic Organisms / Q000737:chemistry; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000302:isolation & purification / Q000494:pharmacology*; D004149:Dioxoles / Q000302:isolation & purification / Q000494:pharmacology*; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010456:Peptides, Cyclic; D044005:Tetrahydroisoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D000077606:Trabectedin; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D004149:Dioxoles; D010456:Peptides, Cyclic; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; C098980:plitidepsin