In search of molecular approaches to improving cancer therapy efficacy.

The study of genome rearrangement sites using full genome sequences is an important approach to revealing the nature of cancer and finding effective ways for cancer treatment. The progress in DNA sequencing could make the procedure of whole genome reading close to routine procedure of lower cost. The personal analysis of rearranged ends (PARE) method used for rearrangement study is reviewed. PARE allows identifying of individual cancer biomarkers making personal medicine possible. Also, the progress in “liquid biopsy” technology based on detection of circulating tumor cells in the patient’s blood is shortly summarized. Another important approach is the discovered phenomenon of synthetic lethality causing cancer cell death due to appropriate combination of mutations in different genes or inhibitors of their protein products. Studies of genome rearrangements and synthetic lethality are Obviously, there comes a time in oncology speaking in biblical language to “gather stones” and to evaluate the significance of molecular diversity detected in tumor cells. Such a feeling may emerge due to the organization of the first systemic discussion of numerous results obtained in individual cancer treatment. Such discussion was organized by the I st International Congress on personalized treatment of cancer (Controversies in Personalized Oncology Treatment) that took place in Barcelona on 7–10 March, 2013 [1]. Prospects of personalized medicine are mostly based on advances in the study of the individual characteristics of tumor DNA sequences. DNA sequences rearrangements especially frequent in cancer genome could currently be localized allowing the construction of individual patient’s oncomaps. Another important approach is the discovered possibility of the socalled synthetic lethality. This term is related to tumor cell killing with the use of individual molecular combinations targeting activity of special enzymes or induction of mutations. These novel approaches can be somewhat simplified using the so-called “liquid biopsy” as the recently discovered possibility of manipulating with cancer patient DNA and separate circulating tumor cells (CTC) present in blood and possibly in other fluids of the organism. Here we discuss some of the molecular approaches that could improve treatment of cancer patients The study of the individual characteristics of DNA in cancer patients is becoming easier due to new technologies: comparable genome hybridization (CGH) and DNA sequencing called New Generation Sequencing (NGS). Possibility of full genome sequencing allows detecting differences in genetic texts of cancer patients in comparison with the genome of healthy individuals. Such a healthy genome for the comparison purposes is called reference genome or reference assembly using the DNA sequencing data from a number of healthy donors. Useful information can currently be obtained by comparison of a) nucleotide sequences of healthy and cancer genomes of different individuals, b) genomes of normal and malignant cells of the same organism, and c) nucleotide sequences of tumors of different histological types. Thus, the develo ped technologies opened a powerful way for the genetic mapping [2]. Analysis of oncomaps allowed separate the genes carrying cancer-related mutations into two groups: driver and passenger as to whether they do or do not influence the malignant cell reproduction rate and hence the growth of the tumor [3]. Interesting, could the genomic rearrangements present in cancer patient be divided alike?