MDA-9/Syntenin (SDCBP): Novel gene and therapeutic target for cancer metastasis.
Pharmacol Res
; 155: 104695, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32061839
ABSTRACT
The primary cause of cancer-related death from solid tumors is metastasis. While unraveling the mechanisms of this complicated process continues, our ability to effectively target and treat it to decrease patient morbidity and mortality remains disappointing. Early detection of metastatic lesions and approaches to treat metastases (both pharmacological and genetic) are of prime importance to obstruct this process clinically. Metastasis is complex involving both genetic and epigenetic changes in the constantly evolving tumor cell. Moreover, many discrete steps have been identified in metastatic spread, including invasion, intravasation, angiogenesis, attachment at a distant site (secondary seeding), extravasation and micrometastasis and tumor dormancy development. Here, we provide an overview of the metastatic process and highlight a unique pro-metastatic gene, melanoma differentiation associated gene-9/Syntenin (MDA-9/Syntenin) also called syndecan binding protein (SDCBP), which is a major contributor to the majority of independent metastatic events. MDA-9 expression is elevated in a wide range of carcinomas and other cancers, including melanoma, glioblastoma multiforme and neuroblastoma, suggesting that it may provide an appropriate target to intervene in metastasis. Pre-clinical studies confirm that inhibiting MDA-9 either genetically or pharmacologically profoundly suppresses metastasis. An additional benefit to blocking MDA-9 in metastatic cells is sensitization of these cells to a second therapeutic agent, which converts anti-invasion effects to tumor cytocidal effects. Continued mechanistic and therapeutic insights hold promise to advance development of truly effective therapies for metastasis in the future.
Palavras-chave
AMD3100 (Compound CID: 65015); Cancer Metastasis; Dasatinib (Compound CID: 3062316); Docetaxel (Compound CID: 148124); Glioblastoma multiforme; Immunotherapy; MDA-9/Syntenin/SDCBP; Neuroblastoma; Paclitaxel (Compound CID: 36314); Prostate adenocarcinoma; Venetoclax (Compound CID: 49846579); Zoledronic acid (Compound CID: 68740)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinteninas
/
Metástase Neoplásica
/
Neoplasias
Tipo de estudo:
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article