Context.-Echinoderm microtubule-associated proteinlike 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion was shown to be the driver of tumorigenesis in approximately 3% to 5% of patients with non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib. However, no complete agreement regarding the best diagnostic test for identification of ALK rearrangements has been achieved yet.Objective.-To investigate the concordance, sensitivity, and specificity of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and reverse transcription-polymerase chain reaction (RT-PCR) for detection of ALK rearrangements.Design.-Thirty-six prospectively tested patients with NSCLC who had adenocarcinoma and 10 ALK-positive samples were included in the study. All samples were tested by IHC (ALK1 clone, 5A4 clone, D5F3 clone), FISH (LSI ALK Break Apart and ALK FISH Probe), and multiplexed RT-PCR.Results.-Immunohistochemistry staining was successful in all samples. Clone D5F3 showed the best sensitivity and specificity of 100%; clones ALK1 and 5A4 showed sensitivities of 91% with specificity of 100%. Both FISH probes showed concordance with sensitivity and specificity of 100%. Hybridization and RT-PCR were successful in 98% and 93.4% of samples, respectively, with sensitivity of 88% and specificity of 100%. Frequent artifacts leading to misinterpretation were observed with all 3 methodologies.Conclusions.-All 3 methodologies showed good sensitivity, specificity, and concordance, when artifacts were characterized and excluded. However, all ambiguous cases have to be confirmed as ALK rearranged by at least 2 of the 3 methods.

Genetic factors, immune dysfunction, chronic inflammation, and dysbiosis of the intestinal microbiome (IM) are believed to participate in the pathogenesis of colorectal cancer (CRC). The positive role of IM regulation in the treatment of inflammatory bowel disorders is determined by a reduction in the growth of pathogenic bacteria and an increase in the production of anti-inflammatory factors. Currently, the available data suggests that the IM dysregulates the immune response against the tumor in its microenvironment, thus either slowing down or accelerating the efficacy of antitumor therapy. Clinical studies have reported benefits of CRC therapy selected based on IM in improving immune intestinal homeostasis, epithelial barrier functions, and quality of life. Moreover, the specific IM signature may modulate the sensitivity to chemo-and / or radiotherapy, as well as the prognosis in patients with colorectal cancer. In this article, we presented the general challenges of the CRC therapy based on IM data in combination with immunotherapy, and described the future prospects of this approach.

Background. The search and use of new molecular prognostic and predictive markers of efficacy detected by liquid biopsy are aimed at understanding the biology of Carcinomas of Unknown Primary (CUP) and improving results of patient treatment. The review is devoted to advances in scientific and clinical research on this issue.Materials and methods. In order to assess the current state of the problem, a search and analysis of relevant data of the scientific databases PubMed, Medline, RISC was carried out.Results. The scientific rationale for the use of liquid biopsy in clinical practice to improve the treatment of cancer patients with CUP is presented. The results of the use of modern approaches to the analysis of fluid biopsy samples in CUP are presented. In particular, the features of using circulating free DNA, circulating tumor DNA, circulating tumor cells in the analysis are considered. The modern possibilities of determining tissue specificity using liquid biopsy in CUP are discussed. The prospects for the development of liquid biopsy for improving diagnostics, determining the prognosis of the disease, and choosing a strategy for treating CUP and the treatment monitoring have been determined.Conclusion. A review of the literature confirms that modern methods of molecular profiling of tumor cells obtained both as a result of liquid biopsy and tissue biopsies will make a significant contribution to the determination of tissue specificity, molecular characteristics of CUP for a personalized approach in order to improve strategies and treatment outcomes for patients with CUP.

Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина; 115478, Россия, Москва, Кашир ское шоссе, д. 23 Резюме Эрлотиниб-низкомолекулярный ингибитор тирозинкиназного домена EGFR, показавший эффективность в лечении немелкоклеточного рака легкого с активирующей мутацией EGFR. В ряде крупных рандомизированных исследований показано значительное увеличение выживаемости без прогрессирования при применении эрлотиниба и других ингибиторов тирозинкиназ в сравнении со стандартной химиотерапией. При этом различий в общей выживаемости не получено, что обусловлено высокой частотой применения ингибиторов тирозинкиназ в последующих линиях терапии у больных, имевших прогрессирование на фоне химиотерапии первой линии. В то же время приведенное ретроспективное исследование показало очевидное (более чем в два раза) увеличение общей выживаемости пациентов, получавших лечение ингибиторами тирозинкиназ, по сравнению с историческим контролем. Не отмечено существенных различий между ингибиторами тирозинкиназ первого и второго поколения. Мутация Т790М является одним из основных механизмов резистентности к эрлотинибу. При прогрессировании на фоне лечения эрлотинибом при выявлении мутации Т790М эффективен ингибитор тирозинкиназ третьего поколения осимертиниб. Комбинация эрлотиниба с бевацизумабом приводит к увеличению выживаемости без прогрессирования, не влияя на общую выживаемость. Совместное применение химиотерапии и ингибиторов тирозинкиназ требует дальнейшего изучения. Приведен пример длительного эффекта на фоне лечения эрлотинибом у больного немелкоклеточным раком легкого IV стадии с мутацией EGFR. Общая длительность лечения составила 68 мес., включая продолжавшуюся в течение 21 мес на фоне индолентного течения заболевания терапию эрлотинибом в комбинации с бевацизумабом и локальной лучевой терапией на зону прогрессирования (метастаз в ребре).