RESUMO
ABSTRACT: Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), has for long remained a deadly form of cancer characterized by high mortality rates resulting from metastasis to multiple organs. Several factors, including the late manifestation of the disease, partly amplified by lack of efficient screening methods, have hampered the drive to design an effective therapeutic strategy to treat this deadly cancer. Understanding the biology of PDAC progression and identifying critical genes regulating these processes are essential to overcome the barriers toward effective treatment. Metastasis suppressor genes have been shown to inhibit multiple steps in the metastatic cascade without affecting primary tumor formation and are considered to hold promise for treating metastatic cancers. In this review, we catalog the bona fide metastasis suppressor genes reported in PDAC and discuss their known mechanism of action.
Assuntos
Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Neoplasias Pancreáticas/genética , Animais , Carcinogênese/genética , Carcinoma Ductal Pancreático/patologia , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Microambiente Tumoral/genéticaRESUMO
KISS1, a metastasis suppressor gene, has been shown to block metastasis without affecting primary tumor formation. Loss of KISS1 leads to invasion and metastasis in multiple cancers, which is the leading cause of cancer morbidity and mortality. The discovery of KISS1 has provided a ray of hope for early clinical diagnosis and for designing effective treatments targeting metastatic cancer. However, this goal requires greater holistic understanding of its mechanism of action. In this review, we go back into history and highlight some key developments, from the discovery of KISS1 to its role in regulating multiple physiological processes including cancer. We discuss key emerging roles for KISS1, specifically interactions with tissue microenvironment to promote dormancy and regulation of tumor cell metabolism, acknowledged as some of the key players in tumor progression and metastasis. We finally discuss strategies whereby KISS1 might be exploited clinically to treat metastasis.
