Vol 15, No 2 (2013)

The review considers the present-day problems and possibilities of targeted therapy for breast cancer (BC) in relation to the biological subtype of a tumor. The emergence of new clinical data on the targeted drugs and their combinations already used in routine practice and new medications from an arsenal of personalized medicine leads to changes in therapeutic approaches. The review gives great attention to the HER2-positive subtype of BC.There is evidence from clinical trials of pertuzumab and T-DM1, which may alter the standard treatment for HER2-positive BC. The review also considers the predictive value of the recurrence index in the luminal subtype and biological characteristics of triple negative BC.

The prognostic value of p53 nuclear expression in Stage 1 (T1N0M0) breast cancer was studied in 315 women treated in Russia (at the N.N.Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, and at the Clinic of the Russian Medical Academy of Postgraduate Education) in 1985 to 2009. An immunohistochemical assay for determining the expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 and the nuclear expression of p53 receptors was carried out at the Leiden University Medical Center. p53 nuclear expression was found in 14,7% of cases and statistically significantly correlated (p<0,05) with important prognostic factors, such as age less than 40 years; histologic type of infiltrating ductal cancer; high-grade cancer; ER- and PR-negative status; and HER2 overexpression. Analysis of overall and relapse-free survivals in the entire group of patients revealed no prognostic value (p>0,05) of p53 expression for the risk of further progression and death. It was suggested that the negative impact of p53 expression in the entire group might be compensated for by the positive role of adjuvant systemic therapy. Subgroup analysis showed that the patients with p53-positive tumors who did not receive any adjuvant drug treatment had the worst relapse-free and cancer-specific survival rates (p<0,05); this was not seen in the patients on adjuvant systemic treatment. Thus, p53 nuclear expression is a negative prognostic factor in Stage I breast cancer; adjuvant systemic therapy can appear to compensate for the unfavorable impact of the expression of this marker.

Whether it is expedient and safe to add bevacizumab to preoperative treatment regimens for colorectal cancer liver metastases has been remained unclear over many years in spite of the duration of its use in this category of patients. In our trial, incorporation of bevacizumab into preoperative therapy was also accompanied by an increase in disease control and a significant reduction in the risk of disease progression during chemotherapy versus other treatment regimens. Comparison with a subgroup of patients treated with oxaliplatin-based regimens without bevacizumab showed that the significance of their difference disappeared; however, a clear trend persisted in favor of bevacizumab addition. KRAS is the only molecular marker used to select patients for therapy with monoclonal antibodies. Our findings also suggest that particular emphasis should be laid on the KRAS status in patients receiving bevacizumab therapy. Random estimation of the KRAS status in the patients who had undergone successful preoperative therapy and liver resection displayed a clear tendency towards the prevalence of the wide-type gene as compared with population-wide data.

The paper provides a literature review of an update on the molecular genetic basis of inherited syndromes associated with the development of pancreatic neuroendocrine tumors, such as type 1 multiple neuroendocrine neoplasia, von Hippel–Lindau disease, type 1 neurofibromatosis, and tuberous sclerosis.

Antitumor activity of trabectedin as a monotherapy in different solid tumors (soft tissue sarcoma, ovarian cancer, breast cancer, melanoma) contributed to research trabectedin-based drug combinations. Phase I trials were searching for optimal dose and schedule of administration trabectedin and trabectedin-based combinations. This review considers aspects of clinical applications and toxic profile of trabectedin alone and combinations, including a rare adverse event – rhabdomyolysis and data of own experience.

Up to date, therapy of disseminated skin melanoma remains a serious issue. In this review authors describe the main features of melanoma epidemiology, general approaches in the systemic therapy of disseminated forms of the disease. Special attention is paid to molecular-genetic mechanisms in the pathogenesis of melanoma. This publication describes the results of novel BRAF-kinase inhibitor targeted drug vemurafenib clinical trials, its safety profile and adverse reactions management. The authors also discuss the further perspectives for vemurafenib use in the therapy of skin melanoma.

The continuing relevance of anemia in cancer patients is confirmed by the results of recent trials. Decreased hemoglobin levels are shown to lead to not only poorer quality of life, but also to lower survival rates in cancer patients. Today there is evidence that iron deficiency is the most common cause of anemia. This paper considers the mechanisms of iron metabolic disturbances, the diagnosis and treatment of iron deficiency. It gives the results of many clinical trials comparing the efficacy of different iron preparations.