Cancer therapy based on oncogene addiction

Tumor cells contain multiple mutations, yet they often depend on continued expressed of a single oncoprotein for survival. Targeting these proteins has led to dramatic responses. Unfortunately, patients usually progress, through drug resistance or adaptive resistance through reprogramming of signaling networks. The Ras‐MAPK pathway provides examples of these successes and failures, and has revealed unexpected degrees of oncogene addiction and signaling complexity that are likely to be useful lessons for the future of targeted therapy. J. Surg. Oncol. 2011;103:464–467. © 2011 Wiley‐Liss, Inc.

[1]  K. Shokat,et al.  Escape from HER family tyrosine kinase inhibitor therapy by the kinase inactive HER3 , 2007, Nature.

[2]  John G. Collard,et al.  Tiam1-deficiency impairs mammary tumor formation in MMTV-c-neu but not in MMTV-c-myc mice , 2008, Journal of Cancer Research and Clinical Oncology.

[3]  G. Bollag,et al.  Discovery of a novel Raf kinase inhibitor. , 2001, Endocrine-related cancer.

[4]  D. Stokoe,et al.  PTEN in brain tumors , 2008, Expert review of neurotherapeutics.

[5]  Kam Y. J. Zhang,et al.  Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity , 2008, Proceedings of the National Academy of Sciences.

[6]  F. McCormick How blocking Raf activates the MAPK pathway , 2010, Pigment cell & melanoma research.

[7]  F. McCormick,et al.  Cancer targets in the Ras pathway. , 2005, Cold Spring Harbor symposia on quantitative biology.

[8]  A. Joe,et al.  Oncogene addiction. , 2008, Cancer research.

[9]  Takafumi Yoshida,et al.  Spreds, inhibitors of the Ras/ERK signal transduction, are dysregulated in human hepatocellular carcinoma and linked to the malignant phenotype of tumors , 2006, Oncogene.

[10]  Todd R. Golub,et al.  BRAF mutation predicts sensitivity to MEK inhibition , 2006, Nature.

[11]  G. Stamp,et al.  Binding of Ras to Phosphoinositide 3-Kinase p110α Is Required for Ras- Driven Tumorigenesis in Mice , 2007, Cell.

[12]  C. Sawyers,et al.  Cancer: Mixing cocktails , 2007, Nature.

[13]  G. Stamp,et al.  RalGDS is required for tumor formation in a model of skin carcinogenesis. , 2005, Cancer cell.

[14]  Martin A. Nowak,et al.  Dynamics of chronic myeloid leukaemia , 2005, Nature.

[15]  Laura M. Heiser,et al.  Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. , 2009, Cancer research.

[16]  M. Ostland,et al.  Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Y. Geng,et al.  Specific protection against breast cancers by cyclin D1 ablation , 2001, Nature.

[18]  Alcino J. Silva,et al.  Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back , 2010, American journal of medical genetics. Part A.

[19]  C. Sander,et al.  V600EBRAF is associated with disabled feedback inhibition of RAF–MEK signaling and elevated transcriptional output of the pathway , 2009, Proceedings of the National Academy of Sciences.

[20]  J. Soria,et al.  Keratoacanthomas and squamous cell carcinomas in patients receiving sorafenib. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  D. Feldser,et al.  Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma , 2009, Nature.

[22]  C. Sawyers Making progress through molecular attacks on cancer. , 2005, Cold Spring Harbor symposia on quantitative biology.

[23]  Violeta Serra,et al.  Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. , 2008, Cancer research.