TY - JOUR
T1 - Somatic evolution of head and neck cancer - Biological robustness and latent vulnerability
AU - Masuda, Muneyuki
AU - Toh, Satoshi
AU - Wakasaki, Takahiro
AU - Suzui, Masumi
AU - Joe, Andrew K.
N1 - Funding Information:
This review was supported in part by fund from Grants-in-Aid for Scientific Research (C): 21592195 and (C): 24592600 to Muneyuki Masuda. This review is fondly dedicated to our mentor Professor I B Weinstein of glorious memory.
PY - 2013/2
Y1 - 2013/2
N2 - Despite recent advancements in multidisciplinary treatments, the overall survival and quality of life of patients with advanced head and neck squamous cell carcinoma (HNSCC) have not improved significantly over the past decade. Molecular targeted therapies, which have been addressed and advanced by the concept of " oncogene addiction" , have demonstrated only limited successes so far. To explore a novel clue for clinically effective targeted therapies, we analyzed the molecular circuitry of HNSCC through the lens that HNSCC is an evolving system. In the trajectory of this somatic evolution, HNSCC acquires biological robustness under a variety of selective pressures including genetic, epigenetic, micro-environmental and metabolic stressors, which well explains the major mechanism of " escaping from oncogene addiction" . On the other hand, this systemic view appears to instruct us approaches to target latent vulnerability of HNSCC that is masked behind the plasticity and evolvability of this complex adaptive system.
AB - Despite recent advancements in multidisciplinary treatments, the overall survival and quality of life of patients with advanced head and neck squamous cell carcinoma (HNSCC) have not improved significantly over the past decade. Molecular targeted therapies, which have been addressed and advanced by the concept of " oncogene addiction" , have demonstrated only limited successes so far. To explore a novel clue for clinically effective targeted therapies, we analyzed the molecular circuitry of HNSCC through the lens that HNSCC is an evolving system. In the trajectory of this somatic evolution, HNSCC acquires biological robustness under a variety of selective pressures including genetic, epigenetic, micro-environmental and metabolic stressors, which well explains the major mechanism of " escaping from oncogene addiction" . On the other hand, this systemic view appears to instruct us approaches to target latent vulnerability of HNSCC that is masked behind the plasticity and evolvability of this complex adaptive system.
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U2 - 10.1016/j.molonc.2012.10.009
DO - 10.1016/j.molonc.2012.10.009
M3 - Review article
C2 - 23168041
AN - SCOPUS:84872495025
VL - 7
SP - 14
EP - 28
JO - Molecular Oncology
JF - Molecular Oncology
SN - 1574-7891
IS - 1
ER -