Personalized medicine and pharmacogenetic biomarkers: progress in molecular oncology testing

Abstract

In the field of oncology, clinical molecular diagnostics and biomarker discoveries are constantly advancing as the intricate molecular mechanisms that transform a normal cell into an aberrant state in concert with the dysregulation of alternative complementary pathways are increasingly understood. Progress in biomarker technology, coupled with the companion clinical diagnostic laboratory tests, continue to advance this field, where individualized and customized treatment appropriate for each individual patient define the standard of care. Here, we discuss the current commonly used predictive pharmacogenetic biomarkers in clinical oncology molecular testing: BRAF V600E for vemurafenib in melanoma; EML4–ALK for crizotinib and EGFR for erlotinib and gefitinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; ERBB2 (HER2/neu) for trastuzumab in breast cancer; BCR–ABL for tyrosine kinase inhibitors in chronic myeloid leukemia; and PML/RARα for all-trans-retinoic acid and arsenic trioxide treatment for acute promyelocytic leukemia.

Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics

“…Therefore, it is necessary, for efficient treatment, to identify the molecular signatures for each melanoma patient, and to plan personalized treatment. 110 For example, melanoma can be classified into one of two categories depending on whether a BRAF mutation exists, as the BRAF inhibitor vemurafenib is only effective for those with a BRAF mutation. Patients with the BRAF mutation have as high as an 80% response to vemurafenib.…”

Epigenetics and Biomarkers in Lung Cancer: Emerging Blood-Based Molecular Biomarkers for Detection and Monitoring

“…We believe that the co-development of new drugs with companion diagnostics will govern the progress in oncology in the immediate future. The role of companion biomarkers in guiding treatment in patients with cancer has been recently very nicely reviewed (Duffy and Crown 2013;Ong et al 2012;Vincent et al 2012) (Table 3).…”

A rapid MZI-IDA sensor system for EGFR mutation testing in non-small cell lung cancer (NSCLC)

“…Hence, myriad methods as the substitute for the direct sequencing method have been developed to detect commonly known mutations and to screen new mutations of the EGFR in NSCLC patients. Until now, peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp, denaturing high-performance liquid chromatography (dHPLC), scorpion amplified refractory mutation system technology (SARMS) and nano-fluidic digital PCR arrays have been developed for detection of mutant genes at levels of 1-10% (Obradovic and Jurisic, 2012; Ellison et al, 2013;Dufort et al, 2011;Contents Simonetti et al, 2010;O'Brien et al, 2014;Ong et al, 2012). Although these methods have proved effective and sensitive to detect EGFR mutations, they are still labor intensive and may require sophisticated instruments that are not suitable for near-patienttesting (NPT) in clinician's office.…”