Patient-tailored treatments with anti-EGFR monoclonal antibodies in advanced colorectal cancer: KRAS and beyond.

Personalized medicine emphasizes the practice of considering individual patient characteristics as opposed to that centered on standards derived from epidemiological studies which, by definition, do not take into account the variability of individuals within a given population. When applied to oncology, personalized medicine is an even more complex concept because it extends the variability beyond the individual patient to the individual tumor. Indeed, the great genotypic and phenotypic variability (both in primary and metastatic sites of cancer) the development of targeted therapies, and the growing availability of biological assays complicate the scenario of personalized medicine in the oncological field. In this paper we review the results of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy in metastatic colorectal cancer (mCRC) in the context of tumor biology, delineating the future prospects of patient-tailored medicine in this area. In particular, we deal with EGFR inhibition by Cetuximab, a chimeric mouse human IgG1 mAb, and panitumumab, a fully human IgG2 mAb. We discuss the clinical impact of anti-EGFR mAbs on wild-type (WT) KRAS mCRC, also taking into account the feasibility of novel multi-marker approaches to treatment decision-making, aimed at increasing the predictive power of pre-therapy biomarkers. Experimental topics and fields of ongoing research, such as targeting microRNAs (miRNAs) with novel anticancer drugs and epigenetics in CRC are also addressed.

Peripheral blood vs. bone marrow for molecular monitoring of BCR-ABL1 levels in chronic myelogenous leukemia, a retrospective analysis in allogeneic bone marrow recipients.

Molecular monitoring of the BCR-ABL1 transcript in chronic myelogenous leukemia (CML) using quantitative real-time PCR (RQ-PCR) can be performed using either bone marrow (BM) or peripheral blood (PB). However, a recent report by Stock et al. [International Journal of Oncology 28 (2006) 1099] questioned the reliability of PB samples for BCR-ABL1 detection as performed by RQ-PCR. We report a study on 114 CML patients who received allogeneic stem cell transplantation (ASCT), and who were monitored by RQ-PCR using paired samples of BM and PB: the total number of determinations was 428, with a median follow-up after transplant of 8 years. BCR-ABL1 transcript was undetectable or <0.1%, in 106 (49.57%) and 62 (29%) paired determinations, respectively. BCR-ABL1 was >0.1% in 36 (16.8%) paired determinations and was discordant in 10 (4.7%). Agreement between PB and BM results was quantified by the kappa test (k = 0.85; 95% CI 0.76-0.94). This study shows that BCR-ABL1 RQ-PCR monitoring of CML patients after ASCT with PB is concordant with BM in 95.3% of cases, and thus may be used to monitor the disease. This may be relevant when discussing both quality of life issues and the need for post-transplant monitoring with the patient.

Molecular diagnosis and monitoring of chronic myelogenous leukemia: BCR-Abl and more.

The current treatment of chronic myelogenous leukemia (CML) is one of the most successful examples of molecularly targeted therapy in cancer. The identification of the fusion oncogene BCR-ABL allowed the discovery of small molecule inhibitors of its tyrosine kinase activity which, in turn, have literally revolutionized the treatment of this disease. However, large part of a successful clinical management of CML relies on appropriate diagnosis, molecular monitoring and identification of mutations potentially leading to drug resistance. These issues are discussed here together with an overview on how patients treated with tyrosine kinase inhibitors should be monitored.