Target Therapies in Lung Cancer

Targeting intracellular signaling molecules is an attractive approach for treatment of malignancies. In particular lung cancer has reached a plateau regarding overall survival, and target therapies could offer the possibility to improve patients' outcome beyond cytotoxic activity. The goal for target therapies is to identify agents that target tumor-specific molecules, thus sparing normal tissues; those molecules are called biomarkers, and their identification is recommended because it has a predictive value, for example, provides information on outcome with regard to a specific treatment. The increased specificity should lead to decreased toxicity and better activity. Herein we provide an update of the main target therapies in development or already available for the treatment of nonsmall cell lung cancer

Use of complementary and alternative medicine (CAM) in cancer patients. An italian multicenter survey

INTRODUCTION: Complementary and Alternative Medicine (CAM) include a wide range of products (herbs, vitamins, minerals, and probiotics) and medical practices, developed outside of the mainstream Western medicine. Patients with cancer are more likely to resort to CAM first or then in their disease history; the potential side effects as well as the costs of such practices are largely underestimated. PATIENTS AND METHOD: We conducted a descriptive survey in five Italian hospitals involving 468 patients with different malignancies. The survey consisted of a forty-two question questionnaire, patients were eligible if they were Italian-speaking and receiving an anticancer treatment at the time of the survey or had received an anticancer treatment no more than three years before participating in the survey. RESULTS: Of our patients, 48.9% said they use or have recently used CAM. The univariate analysis showed that female gender, high education, receiving treatment in a highly specialized institute and receiving chemotherapy are associated with CAM use; at the multivariate analysis high education (Odds Ratio, (OR): 1.96 95% Confidence Interval, CI, 1.27-3.05) and receiving treatment in a specialized cancer center (OR: 2.75 95% CI, 1.53-4.94) were confirmed as risk factors for CAM use. CONCLUSION: Roughly half of our patients receiving treatment for cancer use CAM. It is necessary that health professional explore the use of CAM with their cancer patients, educate them about potentially beneficial therapies in light of the limited available evidence of effectiveness, and work towards an integrated model of health-care provision

Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy.

Funder: Cancer Research UKSingle-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes

Physician Attitudes and Perceptions of Complementary and Alternative Medicine (CAM): A Multicentre Italian Study

Purpose: Complementary and Alternative Medicine (CAM) interventions are widely used by patients with chronic disorders, including cancer, and may interact with cancer treatment. Physicians are often unaware of this, probably due to poor patient-physician communication on CAM. The purpose of this study was to evaluate physicians' knowledge, attitudes and practice patterns regarding CAM in a survey conducted in Italy. Methods: A questionnaire was administered to 438 physicians (11 Italian hospitals) who predominantly treat patients with chronic disease, to collect personal and professional data and information on attitudes toward CAM and its possible role in Conventional Medicine (CM). Results: Of the 438 participants, most were specialists in oncology (18%), internal medicine (17%), surgery (15%), and radiotherapy (11%). Most worked at university (44%) or research hospitals (31%). Forty-two percent of participants believed that CAM could have an integrative role within CM. Oncologists were the physicians who were best informed on CAM (58%). Physicians working at research institutes or university hospitals had a greater knowledge of CAM than those employed at general hospitals (p < 0.0001), and those who were also involved in research activity had a greater knowledge of CAM than those who were not (p < 0.003). Length of work experience was significantly related to CAM knowledge. Moreover, 55% of participants suggest CAM interventions to their patients and 44% discuss CAM with them. The best-known interventions were acupuncture, Aloe vera and high-dose vitamin C. Conclusion: CAM use by patients with chronic disease and/or cancer has become a topical issue for the scientific community and for physicians. Knowing the reasons that prompt these patients to use CAM and guiding them in their decisions would improve treatment and outcomes and also benefit healthcare systems. Our findings contribute to a greater understanding of CAM knowledge, attitudes, and practice among Italian physicians. Further research is needed to identify the more effective CAM treatments and to work toward an integrated healthcare model

THE ELDERLY PROGNOSTIC INDEX (EPI) PREDICTS EARLY MORTALITY IN OLDER PATIENTS WITH DLBCL. A SUBSTUDY OF THE ELDERLY PROJECT BY THE FONDAZIONE ITALIANA LINFOMI (FIL)

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How much should we sequence? An analysis of the Swiss SARS-CoV-2 surveillance effort.

During the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent-something that is unknown at the time of sequencing-and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.IMPORTANCESwitzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses

Hepatocellular Carcinoma in HIV-infected Patients: Check Ealy, Treat Hard

Purpose. Hepatocellular carcinoma (HCC) is an increasingcause of mortality in HIV-infected patients inthe highly active antiretroviral therapy (HAART) era.The aims of this study were to describe HCC tumorcharacteristics and different therapeutic approaches, toevaluate patient survival time from HCC diagnosis, andto identify clinical prognostic predictors in patients withand without HIV infection.Patients and Methods. A multicenter observationalretrospective comparison of 104 HIV-infected patientsand 484 uninfected patients was performed in four Italiancenters. HCC was staged according to the BarcelonaClinic Liver Cancer (BCLC) criteria.Results. Tumor characteristics of patients with andwithout HIV were significantly different for age, EasternCooperative Oncology Group performance status(PS) score <1, and etiology of chronic liver disease. Despitethe similar potentially curative option rate and better BCLC stage at diagnosis, the median survivaltime was significantly shorter in HIV patients. HIVpatients were less frequently retreated at relapse.Independent predictors of survival were: BCLC stage,potentially effective HCC therapy, tumor dimension <3cm, HCC diagnosis under a screening program, HCC recurrence,and portal vein thrombosis. Restricting the analysisto HIV patients only, all positive prognostic factorswere confirmed together with HAART exposure.Conclusion. This study confirms a significantlyshorter survival time in HIV HCC patients. The lessaggressive retreatment at recurrence approach does notbalance the benefit of younger age and better BCLCstage and PS score of HIV patients. Thus, consideringthe prognosis of HIV HCC patients, effective screeningtechniques, programs, and specific managementguidelines are urgently needed

A statistical framework for assessing pharmacological responses and biomarkers using uncertainty estimates

High-throughput testing of drugs across molecular-characterised cell lines can identify candidate treatments and discover biomarkers. However, the cells’ response to a drug is typically quantified by a summary statistic from a best-fit dose-response curve, whilst neglecting the uncertainty of the curve fit and the potential variability in the raw readouts. Here, we model the experimental variance using Gaussian Processes, and subsequently, leverage uncertainty estimates to identify associated biomarkers with a new Bayesian framework. Applied to in vitro screening data on 265 compounds across 1074 cancer cell lines, our models identified 24 clinically established drug-response biomarkers, and provided evidence for six novel biomarkers by accounting for association with low uncertainty. We validated our uncertainty estimates with an additional drug screen of 26 drugs, 10 cell lines with 8 to 9 replicates. Our method is applicable to any dose-response data without replicates, and improves biomarker discovery for precision medicine