Cancer Biotechnology Genetic Analysis Research. Gene expression profiling (GEP) is a powerful tool to identify genes and pathways that are abnormally expressed in carcinogenesis. While these discoveries improve our understanding of molecular pathogenesis, they can also suggest new therapeutic targets, provide information on the pathways of drug resistance and refine the prognostic classifications.
A major problem in Clinical Oncology is the heterogeneous response of tumor histologically similar to treatments such as cytotoxic chemotherapy. Except for estrogen and progesterone and HER2 (c-erbB-2) expression in breast cancer (for hormone therapy and trastuzumab, respectively), kinase domain mutations in EGFR and amplification genomics in cancer of the lung (in targeted EGFR inhibitors gefitinib or erlotinib) and K-ras mutations in cancer of the colon (no response to EGFR antagonists targeted), there is no other simple molecules that are clinically useful predictors of response for any form of therapy cancer.
Encouraging new data suggest that a prediction of response to chemotherapy or biologically targeted agents is possible by the analysis of gene expression profiles (GEP). With the rapid advances in DNA Microarray Technology and the studies more sophisticated, microarray analysis began to make ways in clinical trials and practices Oncology.
Several examples of the potential application of the GEP in Clinical Oncology are described here to illustrate the utility of this technology in common solid tumors and hematologic malignancies.
Acute leukemia - the first report that GEP may be used to classify tumours analyzed a group of acute leukemias. According to gene expression profiles, leukemia, acute myeloid (AML) could be distinguished from acute lymphoblastic leukemia (all) without information standard histology. Similarly, B-cell against T-cell all could be separated based on GEP. This study was used as proof of the principle according to which the clinically useful classifications could be simply in gene expression profiles. In another report, a case with equivocal histology by standard criteria accurately ranked by analysis of genes, demonstrating the potential usefulness of the GEP beyond the standard histological and immunocytochemical methods.
Others have shown that GEP can distinguish between prognostically important subgroups of children with all adults with AML, in some cases identify those who eventually fail therapy. If these results were confirmed by others, the next logical step is to apply a strategy of more intense initial treatment for these patients, selected on the basis of the GEP.
It also possible to screen for agents capable of inducing the differentiation of Leukemic cells through changes in the GEP. Important caveat is that clinical samples gene expression profiles may differ significantly from those observed in cell lines representing the corresponding leukemia.
Prostate cancer - a potential application of GEP for men to the risk of prostate cancer is the identification of biomarkers that can help select men with an altitude of limit in serum prostate specific antigen (PSA) for biopsy. In addition, GEP could be used to identify men with early stage tumors are intended to reproduce and therefore would benefit from more aggressive treatment.
GEP has been used to identify several (e.g., HEPSINE and pim - 1) genes that are overexpressed in cancer of the prostate benign prostate hyperplasia and normal tissues of the prostate, and some are strongly correlated with the clinical results [25-30]. Investigators found a =3 - fold difference in expression in more than 3000 genes when non-recurring prostate cancers were compared to metastatic tumors.
Cancer of the colon - PRL-3 serine phosphatase is constantly increased in metastatic colorectal cancer compared non-metastatic [31]. The conclusion that the metastatic potential appears to be encoded in the primary dispute the notion that metastases are rare cells that have acquired the ability of metastases.
GEP is under study as a means of improving prognosis and may individualize adjuvant treatment recommendations. An area of intense study is the use of GEP to predict which patients with node-negative resected colon cancer are relatively more at risk of relapse and thus, could benefit from adjuvant chemotherapy, as it is generally recommended for patients with node-positive disease.
Breast cancer - a molecular classification of breast cancer has been proposed based on GEP. Luminal (primarily estrogen receptor positive [ER]), type basal (mainly ER-negative), a normal-looking and erbB2 + (primarily HER - 2 overexpressing, ER-negative) subgroups have been identified and have different prognosis.
A major area of investigation is the use of such molecular profiling to predict response to treatment. GEPS of breast cancers that chemotherapy neoadjuvant (preoperative) best meet (ie, basal type, erbB2 +) differs from those of tumours that does not or resistant.
Analysis of GEP can also distinguish the sporadic breast cancers of those associated with BRCA mutations. Perhaps most importantly, GEP can allow the stratification of the also set of subgroups (ie, those with negative lymph nodes axillary cancer of the breast or grade 2 tumor) in categories separate prognostically. In at least some reports, prediction of outcome by GEP outperforms existing prognostic classification. This topic is discussed in detail elsewhere.
GEP biochip analysis is available in the patients with cancer (the score 21-gene assay, as Oncotype DX recurrence) to quantify the likelihood of a recurrence of breast among newly diagnosed women, ganglionic receptor hormone early stage of cancer. The test is designed to identify women with the risk of recidivism is low enough to justify only the failure of chemotherapy and the use of tamoxifen as adjuvant systemic treatment.
Although commercially available, the advantage of using assays of 21-gene recurrence score (e.g., Oncotype DX) to select adjuvant treatment strategy has not been tested at a possible trial. Such an approach is evaluated in the phase III trial assigning individualized Options for treatment (Rx) (the TAILORx clinical trial), sponsored by the National Cancer Institute and led by the Eastern Cooperative Oncology Group (ECOG). Cancer Biotechnology Genetic Analysis Research
