TY - JOUR
T1 - Oncogene addiction as a foundational rationale for targeted anti-cancer therapy
T2 - Promises and perils
AU - Torti, Davide
AU - Trusolino, Livio
PY - 2011/11
Y1 - 2011/11
N2 - A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that - despite the diverse array of genetic lesions typical of cancer - some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development.
AB - A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that - despite the diverse array of genetic lesions typical of cancer - some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development.
KW - DNA damage
KW - Drug development
KW - Oncogene addiction
KW - Targeted therapies
KW - Tyrosine kinases
UR - http://www.scopus.com/inward/record.url?scp=80155191242&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80155191242&partnerID=8YFLogxK
U2 - 10.1002/emmm.201100176
DO - 10.1002/emmm.201100176
M3 - Article
C2 - 21953712
AN - SCOPUS:80155191242
VL - 3
SP - 623
EP - 636
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 11
ER -