title: Biomarkers for personalized oncology: recent advances and future challenges.
abstract: Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and gastrointestinal tumors; anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALk fusion; HER2/neu blockage in HER2/neu-positive breast cancer; and epidermal growth factor receptors (EGFR) inhibition in EGFR-mutated lung cancer. This review presents the current state of our knowledge of biomarkers in five selected cancers: chronic myeloid leukemia, colorectal cancer, breast cancer, non-small cell lung cancer and melanoma.
authors.affiliation: Thomas Jefferson University, Philadelphia PA 19107. Electronic address: madhu.kalia@jefferson.edu.
authors.forename: Madhu
authors.initials: M
authors.lastname: Kalia
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001943:Breast Neoplasms; D002289:Carcinoma, Non-Small-Cell Lung; D015179:Colorectal Neoplasms; D019389:Cytochrome P-450 CYP2D6 / Q000032:analysis / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis / Q000235:genetics; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D011905:Genes, ras; D014453:Glucuronosyltransferase / Q000032:analysis / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008175:Lung Neoplasms; D008495:Medical Oncology / Q000379:methods / Q000592:standards / Q000639:trends; D008545:Melanoma; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000737:chemistry; D057285:Precision Medicine / Q000379:methods / Q000639:trends; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D012878:Skin Neoplasms; D000099148:UGT1A1 Enzyme
chemical_list: D014408:Biomarkers, Tumor; D019389:Cytochrome P-450 CYP2D6; D042943:Dihydrouracil Dehydrogenase (NADP); D066246:ErbB Receptors; D014453:Glucuronosyltransferase; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000099148:UGT1A1 Enzyme; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human
keywords: Genomic biomarkers; Molecular carcinogenesis; Pharmacogenomics; Protein profiling