TY - JOUR
T1 - DNA Damage Repair Pathways in Cancer Stem Cells
AU - Maugeri-Saccà, Marcello
AU - Bartucci, Monica
AU - De Maria Marchiano, Ruggero
PY - 2012
Y1 - 2012
N2 - The discovery of tumor-initiating cells endowed with stem-like features has added a further level of complexity to the pathobiology of neoplastic diseases. In the attempt of dissecting the functional properties of this uncommon cellular subpopulation, investigators are taking full advantage of a body of knowledge about adult stem cells, as the "cancer stem cell model" implies that tissue-resident stem cells are the target of the oncogenic process. It is emerging that a plethora of molecular mechanisms protect cancer stem cells (CSC) against chemotherapy- and radiotherapy-induced death stimuli. The ability of CSCs to survive stressful conditions is correlated, among others, with a multifaceted protection of genome integrity by a prompt activation of the DNA damage sensor and repair machinery. Nevertheless, many molecular- targeted agents directed against DNA repair effectors are in late preclinical or clinical development while the identification of predictive biomarkers of response coupled with the validation of robust assays for assessing biomarkers is paving the way for biology-driven clinical trials.
AB - The discovery of tumor-initiating cells endowed with stem-like features has added a further level of complexity to the pathobiology of neoplastic diseases. In the attempt of dissecting the functional properties of this uncommon cellular subpopulation, investigators are taking full advantage of a body of knowledge about adult stem cells, as the "cancer stem cell model" implies that tissue-resident stem cells are the target of the oncogenic process. It is emerging that a plethora of molecular mechanisms protect cancer stem cells (CSC) against chemotherapy- and radiotherapy-induced death stimuli. The ability of CSCs to survive stressful conditions is correlated, among others, with a multifaceted protection of genome integrity by a prompt activation of the DNA damage sensor and repair machinery. Nevertheless, many molecular- targeted agents directed against DNA repair effectors are in late preclinical or clinical development while the identification of predictive biomarkers of response coupled with the validation of robust assays for assessing biomarkers is paving the way for biology-driven clinical trials.
KW - DNA damage and repair,
KW - DNA damage and repair,
UR - http://hdl.handle.net/10807/111699
U2 - 10.1158/1535-7163.MCT-11-1040
DO - 10.1158/1535-7163.MCT-11-1040
M3 - Article
SN - 1535-7163
SP - 1627
EP - 1636
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
ER -