Applications of Biomarkers for Cancer Diagnosis and Therapy

Role of biomarkers is increasingly promising with new targeted therapies for cancer, suggesting an integrated approach using the genetic make-up of the tumor and the genotype of the patient for treatment selection and patient management. The effectiveness of the Bcr-Abl kinase inhibitor imatinib (Novartis’ Gleevec) in chronic myeloid leukemia (CML) and in a subset of patients with acute lymphoblastic leukemia (ALL) reduces with advancing disease and/or the development of resistance to imatinib. Tasigna® (Novartis) inhibits proliferation of hematopoietic cells expressing the mutants in Ph+ CML and ALL and is also effective against several imatinib-resistant Bcr-Abl mutants; it is combined with a battery of tests to define which patients should receive it.

Biomarkers can aid in patient stratification (risk assessment), treatment response identification (surrogate markers), or in differential diagnosis (identifying individuals who are likely to respond to specific drugs). To be clinically useful, a biomarker must favorably affect clinical outcomes such as decreased toxicity, increased overall and/or disease-free survival, or improved quality of life. Once the methods for assessment of the biomarker are established and the initial results show promise with regard to the predictive ability of a biomarker, it may be possible to achieve the goal of ‘predictive oncology’. New drugs in oncology are being pursued with parallel development of a biomarker-based diagnostic test. As genotyping of drug- metabolizing enzymes becomes more widespread in the future, more changes are expected in drug labels.

Modern tumor pathology is now viewed at the molecular level ranging from immunohistochemistry (IHC) biomarkers, to gene signature classifiers and gene mutations, all of which provide crucial information about which patients will respond to targeted therapy regimens. An excellent review discusses the general types of targeted therapies used in a clinical setting and provides a short background on IHC, gene expression and DNA sequencing technologies (Tobin et al. 2015). The authors also highlight several strategies that are pivotal to the successful development of targeted anticancer drugs. Table 13.4 shows cancer biomarkers used for diagnosis and therapy.

Table 13.4 Cancer biomarkers used for diagnosis and therapy

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