Biopsia Líquida en Oncología: ¿Mito o Realidad? Liquid Biopsy in Oncology: Myth or Reality?

One of the most relevant challenge in oncology would be the ability to deeply know tumoral genetic aspects through technological innovation and translational research to be finally able to personalize oncological treatment based not only on classical patient’s clinical characteristics but also on its tumoral genetic portrait. In the last few years, many studies showed that to select cancer patients for a specific drug on the basis of specific genetic alterations could determine the greatest potential clinical benefit for a longer time, compared to treatment with the classic cytotoxic chemotherapy. Thus, oncology moves from the classic "one size fits all" approach, which provided classic chemotherapy agents on the basis of the cancer primary site and its histological type, to a new classification based on the tumor molecular profile. The characterization of the genetic alterations of the tumors, and the understanding of the complex interaction between the molecules of the same network represents, therefore, the rationale on which precision medicine is based. These advances have been made possible by the recent development of new technologies, such as next generation sequencing (NGS) or massive parallel sequencing (MPS), which allow the sequencing of larger gene portions compared to previous technologies, with reduced times and an increase in analytical sensitivity.Uno de los desafíos más relevantes en oncología sería la capacidad de conocer profundamente los aspectos genéticos tumorales a través de la innovación tecnológica y la investigación traslacional para finalmente poder personalizar el tratamiento oncológico basado no solo en las características clínicas del paciente clásico sino también en su retrato genético tumoral. En los últimos años, muchos estudios mostraron que seleccionar pacientes con cáncer para un fármaco específico sobre la base de alteraciones genéticas específicas podría determinar el mayor beneficio clínico potencial durante más tiempo, en comparación con el tratamiento con la quimioterapia citotóxica clásica. Por lo tanto, la oncología pasa del enfoque clásico de "talla única", que proporcionó agentes de quimioterapia clásicos en función del sitio primario del cáncer y su tipo histológico, a una nueva clasificación basada en el perfil molecular del tumor. La caracterización de las alteraciones genéticas de los tumores y la comprensión de la interacción compleja entre las moléculas de la misma red representa, por lo tanto, la razón en que se basa la medicina de precisión. Estos avances han sido posibles gracias al reciente desarrollo de nuevas tecnologías, como la secuenciación de próxima generación (NGS) o la secuenciación paralela masiva (MPS), que permiten la secuenciación de porciones genéticas más grandes en comparación con tecnologías anteriores, con tiempos reducidos y un aumento en Sensibilidad analítica

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status.Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Materials and methods: Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected, according to the PRISMA guidelines. Pooled HRs were calculated for both the OS and/or RFS. Results: Seven eligible trials (1403 patients) were included. Pooled analysis showed that KRAS mutations predicted a significantly worse both RFS (HR: 1.65; 95% CI: 1.23-2.21) and OS (HR: 1.86; 95% CI: 1.51-2.30) in patients who underwent surgical resection of CLM. BRAF mutations were also associated with a significantly worse OS (HR: 3.90; 95% CI: 1.96-7.73) in this subgroup of patients. Conclusions: This meta-analysis suggests both KRAS and BRAF mutations as poor, prognostic biomarkers, associated with worse survival outcomes, in patients undergoing hepatic resection of CLM

Factors associated with metabolic syndrome in a Mediterranean population : role of caffeinated beverages

BACKGROUND: Intake of caffeinated beverages, such as coffee and tea, has been related to improvements in components of metabolic syndrome (MetS), but studies conducted in the Mediterranean region are scarce. The aim of this study was to evaluate whether or not consumption of a variety of beverages containing caffeine was associated with components of MetS in an Italian population. METHODS: From May 2009 to December 2010, a cross-sectional survey was conducted on 1889 inhabitants living in Sicily, southern Italy. Data regarding demographic characteristics, habitual beverage intake, and adherence to the Mediterranean diet were collected, and clinical information was retrieved from the general practitioners’ computer records. RESULTS: After adjusting for all covariates, coffee (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.27–0.70) and tea (OR 0.51, 95% CI 0.34–0.78) were associated with MetS, whereas no association was observed between caffeine intake and MetS. Among other factors, age, body mass index, physical activity, current smoking, and adherence to Mediterranean diet were associated with having MetS. Triglycerides were inversely associated with consumption of both espresso coffee and tea. The healthy effects of such beverages were more evident in individuals with unhealthy dietary habits. CONCLUSIONS: Although no direct association between caffeine intake and MetS or its components was observed, coffee and tea consumption was significantly related to reduced odds of MetS

Looking for the best immune-checkpoint inhibitor in pre-treated NSCLC patients: An indirect comparison between nivolumab, pembrolizumab and atezolizumab

Immune-checkpoint inhibitors represent the new standard of care in patients with advanced NSCLC who progressed after first-line treatment. This work aim to assess any difference in both efficacy and safety profiles among Nivolumab, Pembrolizumab and Atezolizumab in pre-treated NSCLC patients. Randomized clinical trials comparing immune-checkpoint inhibitor versus docetaxel in pre-treated patients with advanced NSCLC were included and direct comparison meta-analysis of selected trials have been performed. Subsequently the summary estimates of Nivolumab, Pembrolizumab and Atezolizumab emerging from the direct meta-analysis were selected to provide the pooled estimates of hazard ratio (HR) and relative risk (RR) for the indirect comparisons among these agents. A total of 5 studies met the selection criteria and were included in the meta-analysis. Indirect comparisons for efficacy outcomes showed the RR for ORR nivolumab versus atezolizumab 1.66 (95% CI 1.07â2.58), pembrolizumab versus atezolizumab 1.94 (95% CI 1.30â2.90). No significant differences in both PFS and OS have been observed. Indirect comparisons for safety showed the RR for G3-5 AEs nivolumab versus pembrolizumab 0.41 (95% CI 0.29â0.60), nivolumab versus atezolizumab 0.50 (95% CI 0.35â0.72). No significant differences in both pneumonitis and discontinuation rate have been observed. The results of this work revealed that nivolumab and pembrolizumab are associated with a significant increase of ORR as compared to atezolizumab and nivolumab is associated with a significant lower incidence of G3-5 AEs as compared to the other drugs. These evidences could support the oncologists to select the best drug for each patient

Association between polyphenol intake and adherence to the Mediterranean diet in Sicily, southern Italy

Abstract Background Mediterranean diet has been demonstrated to exert beneficial effects toward various health outcomes. Among the compounds that may be responsible for such benefits, polyphenols have been proposed as potential candidates. The aim of this study was to evaluate whether dietary polyphenols were associated with adherence to the Mediterranean diet in a Sicilian cohort. Methods A total of 1937 adults were recruited in the urban area of Catania, southern Italy. Background characteristics and dietary habits were collected through validated questionnaires. Adherence to the Mediterranean diet was evaluated through application of a validated score (MEDI-LITE score). Dietary intake of polyphenols was estimated through the Phenol-explorer database. Differences in mean intake between quartiles of the MEDI-LITE score and association between quartiles of polyphenol intake and high adherence to the Mediterranean diet (highest quartile of the score) were calculated though logistic regression analyses. Results Mean intake of most polyphenols was significantly different between quartiles of the MEDI-LITE score, being generally higher in individuals more adherent to the Mediterranean diet. Only few compounds, such as lignans, anthocyanins, and flavanones, showed a linear positive association with high adherence to the Mediterranean diet, while other polyphenol classes were associated in a non-linear manner. Among individual polyphenols, apigenin, hesperetin, naringenin, lariciresinol, matairesinol, pinoresinol, secoisolariciresinol, and ferulic acid were associated with high adherence to Mediterranean diet in a linear manner, while all the others (except for myricetin) were associated in a non-linear way. Conclusions Mean polyphenol intake was higher in individuals more adherent to the Mediterranean diet compared to less adherent. However, dietary sources of polyphenols not included in the traditional foods comprised in the Mediterranean diet may contribute to total and specific classes of polyphenols irrespectively of their inclusion within the context of the Mediterranean diet

The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials

Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22â1.02). No significant difference was shown in term of tSRE (HR 0.99, 95% CI 0.83â1.17). In conclusion, abiraterone and enzalutamide have both demonstrated to significantly delay the bone progression resulting in similar improvements in bone-related endpoints in patients with mCRPC

A narrative review on the implementation of liquid biopsy as a diagnostic tool in thoracic tumors during the COVID-19 pandemic

Objective: In this review, we evaluate the role of liquid biopsy in managing lung cancer patients during the still ongoing coronavirus disease 2019 (COVID-19) healthcare emergency. Background: The novel influenza coronavirus (severe acute respiratory syndrome coronavirus or SARSCoV-2) has upended several aspects of our lives, including medical activities. In this setting, many routine cancer diagnostic and therapeutic procedures have been suspended, leading to delays in diagnosis, treatments, and, ultimately, increases in cancer mortality rates. Equally drastic has been the impact of COVID-19 on clinical trials, many of which have been stalled or have never begun. This has left many patients who were hoping to receive innovative treatments in a limbo. Although, as of today, the introduction of drastic security measures has been crucially important to contain the pandemic, one cannot ignore the need to continue providing chronically ill patients all the health care they need, in terms of detection, prevention, and treatment. In these unprecedented times, liquid biopsy, more than ever before, may play a relevant role in the adequate management of these frail patients. Methods: we performed a deep analysis of the recent international literature published in English on PUBMED in the last six months focused on the impact of SARS-CoV-2 on the management of lung cancer patients, focusing the attention on the role of liquid biopsy. Conclusions: COVID-19 pandemic has significantly modified our lives and overall medical practice. In these unprecedented times, liquid biopsy may represent a valid and less time-consuming diagnostic approach than conventional tissue and cytological specimens

Triple negative breast cancer: Shedding light onto the role of pi3k/akt/mtor pathway

Breast cancer is one of the most widespread carcinoma and one of the main causes of cancer-related death worldwide, especially in women aged between 35 and 75 years. Among the different subtypes, triple negative breast cancer (TNBC) is characterized by the total absence of the estrogen-receptor (ER) and progesteron-receptor (PR) expression as well as the lack of human epidermal growth factor receptor 2 (HER2) overexpression or gene amplification. These biological characteristics confer to TNBC a higher aggressiveness and relapse risk along with poorer prognosis compared to other subtypes. Indeed, 5-years survival rate is still low and almost all patients die, despite any adjuvant treatment which at moment represents the heading pharmacological approach. To date, several clinical trials have been designed to investigate the potential role of some molecular markers, such as VEGF, EGFR, Src and mTOR, for targeted treatments in TNBC. In fact, many inhibitors of the PI3K/AKT/mTOR pathway, frequently de-regulated in TNBC, are acquiring a growing interest and several inhibitors are in preclinical development or already in early phase clinical trials. In this Review, we investigated the role of the PI3K/AKT/mTOR pathway in TNBC patients, by summarizing the molecular features that led to the distinction of different histotypes of TNBC. Furthermore, we provided an overview of the inhibition mechanisms of the mTOR and PI3K/AKT signaling pathways, highlighting the importance of integrating biological and clinical data for the development of mTOR inhibitors in order to implement targeted therapies for TNBC patients

Dietary restriction: could it be considered as speed bump on tumor progression road?

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyzed for BE diagnosis. Quantitative Real-time PCR was used to compare miRNA expression levels in serum and 60 disease/ normal-paired tissues from 30 patients diagnosed with esophagitis, columnar-lined oesophagus (CLO) or BE. MiRNA expression analysis showed that miR-143, miR-145, miR-194 and miR-215 levels were significantly higher, while miR-203 and miR-205 were lower in BE tissues compared with their corresponding normal tissues. Esophageal mucosa analysis of patients with CLO and esophagitis showed that these miRNAs were similarly deregulated but to a lesser extent keeping the same trend and CLO appeared as intermediate step between esophagitis and BE. Analysis on circulating miRNA levels confirmed that miR-194 and miR-215 were significantly upregulated in both BE and CLO compared to esophagitis, while miR-143 was significantly upregulated only in the Barrett group. These findings suggest that miRNAs may be involved in neoplastic/ metaplastic progression and miRNA analysis might be useful for progression risk prediction as well as for monitoring of BE/CLO patients