There has been enthusiasm that the addition of the targeted agents cetuximab, panitumuman and bevacizumab to chemotherapy can improve overall survival (OS) of patients with colorectal cancer (CRC).

However, latest clinical and genomics data limit now the expectations. Studies showed an improvement in progression-free survival (PFS) only in KRAS wild-type metastatic CRC. But the absence of OS benefit and in fact retrospective analysis of specimens from randomized trials on KRAS status, suggest caution on true therapeutic effects of these agents.

This perspective provides a comprehensive analysis of the results from clinical trials evaluating the efficacy and adverse effects of these targeted drugs in the systemic treatment of mCRC. It is also discussed the molecular mechanisms underlying CRC induction and metastasis that explain the resistance to these drugs. Moreover, considering the complexity and heterogeneity of the disease revealed by studies using next-generation DNA sequencing technology, it is described how efforts to complete the CRC somatic mutations catalogue, to provide insights how Wnt signaling pathway, beyond EGFR and VEGF pathways, has crucial role in CRC and to understand complex gene-gene, intratumoral cell-cell interactions and signaling pathways networks through molecular networks can create a future new generation of networks-based development of biologically targeted agents

Comparative-effectiveness research (CER) is the current gold standard for improving health care. New products including drugs, medical devices, diagnostics, biomarkers and therapeutics should be proven more effective and safe as compared to standards that are used in a day-to-day clinical practice. International and national Organizations or Agency, such as FDA require rigorous criteria for approval of new diagnostics and therapeutics usually met in large randomized controlled trials. However, such an evaluation does not consider differences in therapy response and adverse effects among patients with same disease who receive the same treatment.

Based on the recent DNA sequencing technology explosion that reveals a widespread genetic variation among patients, a similar explosion over the last few years has been occurred on research for personalized medicine. Aim is to discover those causal mutations characteristic for each patient, which will allow the development of specific individualized therapies. However, there is critique that it is too early for personalized diagnostics and therapeutic approaches and this human genome heterogeneity-based research requires major costs and funding with uncertain effectiveness.

This perspective article discusses strengthens and weaknesses of CER and personalized medicine for improving health care. It is particularly considered costs, funding priorities by agencies and potential harms for the population when very expensive new targeted therapies, for example in cancer treatment, are promoted by industry in the pharmaceutical market with uncertain effectiveness and safety.

Laparoscopic low anterior resection can improve outcomes of patients with rectal cancer. Although total mesorectal excision has been the standard surgery, controversial issues including distal-free resection margin, prophylactic stoma of anastomosis and preoperative chemoradiotherapy are discussed here.

Advances in the early detection of gastroesophageal cancer through screening endoscopy and treatment are faster in Japan than in the USA and Europe. Here it is discussed a clinical success in Japan with early detection of malignant lesions in gastric tube after esophagectomy and if such approaches are feasible in the Western world.

Yet 10 years after the first complete human genome sequence and the current revolution in the next-generation DNA sequencing technology, clinical applications in the prevention and treatment of major diseases such as cardiovascular disorders and cancer are limited.

As costs rapidly drop and quality of DNA sequence data is improved, with published two dozens of complete human genome sequence, 200 unpublished and thousands human and cancer genomes to be completed in the next few years, important insights into genetic and genomic variation underlying physiological and pathological cellular processes will emerge. In this era of “big” biology and science, when and how we will see clinical success? Genome leaders such as Collins and Venter emphasize that practical personalized medicine passes through mutations' catalogue completion and consideration of phenotype respectively.

This perspective article describes challenges in understanding genotype-phenotype map and the need for systems biology and medicine to predict complex interactions among biological and environmental systems. The next bigger challenge is how to discover those certain somatic “point“ mutations, genomic rearrangements and copy-number changes which after interactions each to other and with lifestyle factors drive pathogenesis, diseases risk and response to therapy. It is also here described how integration of genomic revolution data along with multiple clinical (phenotype) data in powerful computational and mathematical network modeling and strategies can lead to genomics medicine revolution

Gastric cancer is one of the most deadly cancers in the world. Early diagnosis and treatment are effective for improving the survival rate of gastric cancer, but there is a shortage of specific probes for molecular signatures. To identify the biomarkers on gastric cancer cell surface sensitively, we selected DNA aptamers against gastric cancer cell (SGC-7901) by cell systematic evolution of ligands by exponential enrichment (cell-SELEX), and validate their affinity and specificity for SGC-7901 cells. This research started with the synthesis of an 88 nucleotides (nt) single strand DNA (ssDNA) library containing a random sequence of 52 nucleotides flanked by 5' and 3' fixed regions of 18 nucleotides. SGC-7901 cells were acted as target and human gastric mucosa cells were acted as counter-target by establishing a simpler cell-SELEX technology, which we acted living cells as screen media directly, optimized PCR amplification protocols and applied biotin-streptavidin system to prepare the secondary ssDNA library. After 12 rounds of SELEX screening, the aptamers against SGC-7901 cells were enriched to a considerable degree, the binding affinity of random ssDNA pool with target cells increased to a steady state. PCR products of the last round were cloned and sequenced. There were four aptamers have the absolute identical sequence, binding assays indicated that this aptamer sequence had the highest affinity and specificity to SGC-7901 cells. The DNA aptamer as probes against SGC-7901 cells with high affinity and high specificity were obtained, it can provide an effective approach for gastric cancer diagnosis and therapy.

The significance of standardized surgery with appropriate resection both the primary tumor and the regional lymph nodes in improving outcomes of patients with colorectal cancer are described in this report.

Although cure is achievable in small breast cancer, a subgroup of women faces a recurrence risk. This article discusses advances and limitations in predicting this high-risk group, whether trastuzumab for small, HER2-positive tumors can reduce recurrence risk. New research directions including cancer stem cells and molecular networks are also described.