TY - JOUR
T1 - ERK1/2 and p38α/β signaling in tumor cell quiescence
T2 - Opportunities to control dormant residual disease
AU - Sosa, Maria Soledad
AU - Avivar-Valderas, Alvaro
AU - Bragado, Paloma
AU - Wen, Huei Chi
AU - Aguirre-Ghiso, Julio A.
PY - 2011/9/15
Y1 - 2011/9/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-10-2574
DO - 10.1158/1078-0432.CCR-10-2574
M3 - Review article
C2 - 21673068
AN - SCOPUS:80052867880
SN - 1078-0432
VL - 17
SP - 5850
EP - 5857
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -