title: DNA damage repair pathways in cancer stem cells.
abstract: 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.
authors: Department of Hematology Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy. maugeri.marcello@gmail.com
authors: Marcello
authors: M
authors: Maugeri-Saccà
authors: Monica
authors: M
authors: Bartucci
authors: Ruggero
authors: R
authors: De Maria
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents