title: [Contribution to tumor escape and chemotherapy response: A choice between senescence and apoptosis in heterogeneous tumors].
abstract: Understanding adaptive signaling pathways in response to chemotherapy is one of the main challenges of cancer treatment. Activated in response to DNA damage, cell cycle and mitotic checkpoints activate the p53-p21 and p16-Rb pathways and induce apoptosis or senescence. Since senescent cells survive and produce a secretome that influences neighbouring cells, it is not particularly clear whether these responses are equivalent and if tumor cells escape these two suppressive pathways to the same extent. Predicting escape is also complicated by the fact that cancer cells adapt to treatments by activating the epithelial-mesenchymal transition and by producing clones with cancer-initiating cells features. Dedifferentiation pathways used in stressful conditions reconstitute dividing and sometimes more aggressive populations in response to chemotherapy. These observations illustrate the importance of tumor heterogeneity and the adaptation capacities of different intra-tumoral subclones. Depending on their oncogenic profile, on their localisation within the tumor and on their interaction with stromal cells, these subclones are expected to have different responses and adaptation capacities to chemotherapy. A complete eradication will certainly rely on combination therapies that can kill at the same time the bulk of the sensitive tumor but can also prevent plasticity and the generation of persistent clones.
authors.affiliation: Paul-Papin ICO Cancer Center, Inserm U892, CNRS 6299, Angers University, 15, rue André-Boquel, 49055 Angers, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jonchère
authors.affiliation: Paul-Papin ICO Cancer Center, Inserm U892, CNRS 6299, Angers University, 15, rue André-Boquel, 49055 Angers, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vétillard
authors.affiliation: Paul-Papin ICO Cancer Center, Inserm U892, CNRS 6299, Angers University, 15, rue André-Boquel, 49055 Angers, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toutain
authors.affiliation: Paul-Papin ICO Cancer Center, Inserm U892, CNRS 6299, Angers University, 15, rue André-Boquel, 49055 Angers, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Guette
authors.affiliation: Paul-Papin ICO Cancer Center, Inserm U892, CNRS 6299, Angers University, 15, rue André-Boquel, 49055 Angers, France. Electronic address: olivier.coqueret@univ-angers.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Coqueret
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D054337:Cell Dedifferentiation; D002470:Cell Survival; D016922:Cellular Senescence / Q000502:physiology*; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008938:Mitosis / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D019139:Tumor Escape; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins
keywords: Apoptose; Apoptosis; Cancer colorectal; Chemotherapy; Chimiothérapie; Colorectal cancer; Drug resistance; Heterogeneity; Hétérogénéité; Résistance; Senescence; Sénescence