title: ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease.
abstract: Systemic minimal residual disease after primary tumor treatment can remain asymptomatic for decades. This is thought to be due to the presence of dormant disseminated tumor cells (DTC) or micrometastases in different organs. DTCs lodged in brain, lungs, livers, and/or bone are a major clinical problem because they are the founders of metastasis, which ultimately kill cancer patients. The problem is further aggravated by our lack of understanding of DTC biology. In consequence, there are almost no rational therapies to prevent dormant DTCs from surviving and expanding. Several cancers, including melanoma as well as breast, prostate, and colorectal carcinomas, undergo dormant periods before metastatic recurrences develop. Here we review our experience in studying the cross-talk between ERK1/2 and p38α/β signaling in models of early cancer progression, dissemination, and DTC dormancy. We also provide some potential translational and clinical applications of these findings and describe how some currently used therapies might be useful to control dormant disease. Finally, we draw caution on the use of p38 inhibitors currently in clinical trials for different diseases as these may accelerate metastasis development.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Tisch Cancer Institute at Mount Sinai, New York, New York, USA.
authors.forename: Maria Soledad
authors.initials: MS
authors.lastname: Sosa
authors.forename: Alvaro
authors.initials: A
authors.lastname: Avivar-Valderas
authors.forename: Paloma
authors.initials: P
authors.lastname: Bragado
authors.forename: Huei-Chi
authors.initials: HC
authors.lastname: Wen
authors.forename: Julio A
authors.initials: JA
authors.lastname: Aguirre-Ghiso
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048290:Mitogen-Activated Protein Kinase 11 / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018365:Neoplasm, Residual; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases