New approach to cancer therapy based on a molecularly defined cancer classification

Translational and clinical cancer research, as well as clinical trials and treatment of cancer, are essentially structured based on the organ in which tumors originate. However, the recent explosion of knowledge about the molecular characteristics of tumors is opening a new way to tackle cancer. This article proposes a different approach to the classification of cancer with important implications for treatment and for basic, translational, and clinical research. The authors postulate that cancers from diverse organs of origin with similar molecular traits should be managed together. The common molecular features observed in different tumors determine clinical actions in a better way than organ‐based classification. Thus, comparisons between tumors residing in different locations but with shared molecular characteristics will improve the therapeutic approach and the understanding of the biology of cancer. CA Cancer J Clin 2014;64:70–74. © 2013 American Cancer Society.

[1]  M. Nowak,et al.  Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer , 2010, Nature.

[2]  A. Jimeno,et al.  HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  I. Weinstein Addiction to Oncogenes--the Achilles Heal of Cancer , 2002, Science.

[4]  Ruud H. Brakenhoff,et al.  Detection, clinical relevance and specific biological properties of disseminating tumour cells , 2008, Nature Reviews Cancer.

[5]  K. A. Gelmon Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial , 2011 .

[6]  Mark Robson,et al.  Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial , 2010, The Lancet.

[7]  S. O’Day,et al.  Utility of Circulating B-RAF DNA Mutation in Serum for Monitoring Melanoma Patients Receiving Biochemotherapy , 2007, Clinical Cancer Research.

[8]  A. Ullrich,et al.  p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor , 1989, Molecular and cellular biology.

[9]  A. Tutt,et al.  Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial , 2010, The Lancet.

[10]  M. Ladanyi,et al.  Epidermal Growth Factor Receptor Mutation Testing in Lung Cancer: Searching for the Ideal Method , 2007, Clinical Cancer Research.

[11]  Daniel A. Haber,et al.  Epidermal growth factor receptor mutations in lung cancer , 2007, Nature Reviews Cancer.

[12]  Y. Yatabe,et al.  Highly Sensitive Detection of EGFR T790M Mutation Using Colony Hybridization Predicts Favorable Prognosis of Patients with Lung Cancer Harboring Activating EGFR Mutation , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[13]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[14]  D N Shapiro,et al.  Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. , 1994, Science.

[15]  S. Nelson,et al.  Melanoma whole exome sequencing identifies V600EB-RAF amplification-mediated acquired B-RAF inhibitor resistance , 2012, Nature Communications.

[16]  J. Cheville,et al.  ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients , 2012, Modern Pathology.

[17]  Lin Huan,et al.  Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer , 2010 .

[18]  H. Aburatani,et al.  Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer , 2007, Nature.

[19]  D. Tuveson,et al.  Suppression of BRAF(V599E) in human melanoma abrogates transformation. , 2003, Cancer research.

[20]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[21]  S. Goodman,et al.  Circulating mutant DNA to assess tumor dynamics , 2008, Nature Medicine.

[22]  Jorge S. Reis-Filho,et al.  Resistance to therapy caused by intragenic deletion in BRCA2 , 2008, Nature.

[23]  Andrew Menzies,et al.  The patterns and dynamics of genomic instability in metastatic pancreatic cancer , 2010, Nature.

[24]  A. McCullough RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors , 2013 .

[25]  D. Cunningham,et al.  Targeting the human EGFR family in esophagogastric cancer , 2011, Nature Reviews Clinical Oncology.

[26]  Yoon-Koo Kang,et al.  Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial , 2010, The Lancet.

[27]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[28]  Kris Chang,et al.  Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. , 2012, The New England journal of medicine.

[29]  Heather L. Miller,et al.  A molecular fingerprint for medulloblastoma. , 2003, Cancer research.

[30]  F. Cappuzzo,et al.  HER2 mutation and response to trastuzumab therapy in non-small-cell lung cancer. , 2006, The New England journal of medicine.

[31]  Aleksandar Sekulic,et al.  Efficacy and safety of vismodegib in advanced basal-cell carcinoma. , 2012, The New England journal of medicine.

[32]  Q. Gu,et al.  Activating Smoothened mutations in sporadic basal-cell carcinoma , 1998, Nature.

[33]  D. Livingston,et al.  In search of the tumour-suppressor functions of BRCA1 and BRCA2 , 2000, Nature.

[34]  Sung-Bae Kim,et al.  Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. , 2012, The New England journal of medicine.

[35]  Johannes G. Reiter,et al.  The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers , 2012, Nature.

[36]  J. Dungan Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial , 2011 .

[37]  J. Isola,et al.  Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[38]  R. Myers,et al.  Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome , 1996, Science.

[39]  Raoul Tibes,et al.  Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. , 2009, The New England journal of medicine.

[40]  H. Mano ALKoma: a cancer subtype with a shared target. , 2012, Cancer discovery.

[41]  Joon-Oh Park,et al.  MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling , 2007, Science.

[42]  H. Varmus,et al.  Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain , 2005, PLoS medicine.

[43]  Enzo Medico,et al.  Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer , 2012, Nature.

[44]  Michael Dean,et al.  Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome , 1996, Cell.