Molecular genetic tools shape a roadmap towards a more accurate prognostic prediction and personalized management of cancer

Abstract

The continuous flow of molecular genetic information has cautiously started integrating into clinical practice changing the future landscape of the clinical management of cancer. Germline mutation analysis for individuals at familial risk and testing result-based surgical or nonsurgical preventive intervention can protect from hereditary breast-ovarian, colorectal and stomach cancer and reduce mortality. Research is focusing now on the development of effective chemoprevention to replace prophylactic surgery for improving quality of life and to provide novel targeted therapies for hereditary cancer patients. The TNM staging system and conventional clinicopathologic factors have led clinical decisions on adjuvant therapy for decades improving survival in patients with early-stage tumors. However, current staging methods and therapeutic decisions remain suboptimal. Patients with early-stage cancer who are at low risk of recurrence could be spared the toxicity of systemic treatment if clearly distinguished, while others at high risk of distant recurrence could get maximal benefit if therapy matched the molecular genetic profile of either the host or the tumor. With the establishment of validated molecular analysis techniques it is believed that clinical biomarkers will gradually overtake TNM by their capacity to form more accurate prognostic systems and delineate better predictors of response to specific therapies. Areas of cancer research such as germ-cell mutation analysis, tumor gene-signature identification, gene expression profile linked targeted therapy, cancer stem cells, circulating cancer cells and single-nucleotide polymorphism keep on producing promising data which is believed to refine future preventive and early intervention strategies on an individual basis. Today these gene-based strategies are in a transition phase prior to full implementation into clinical practice. At present they wait for the results of large-scale prospective validation studies which compare molecular against "classic" markers. It is anticipated that molecular genetic biomarkers when implemented in clinical practice will considerably improve both biologically guided therapeutic decisions and clinical outcomes. ©2007 Landes Bioscience.