International Agency for Research on Cancer

About: International Agency for Research on Cancer is a government organization based out in Lyon, France. It is known for research contribution in the topics: Cancer & Population. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

Heterogeneous mechanisms of primary and acquired resistance to third-generation EGFR inhibitors

Abstract: Purpose: To identify novel mechanisms of resistance to third-generation EGFR inhibitors in patients with lung adenocarcinoma that progressed under therapy with either AZD9291 or rociletinib (CO-1686). Experimental Design: We analyzed tumor biopsies from seven patients obtained before, during, and/or after treatment with AZD9291 or rociletinib (CO-1686). Targeted sequencing and FISH analyses were performed, and the relevance of candidate genes was functionally assessed in in vitro models. Results: We found recurrent amplification of either MET or ERBB2 in tumors that were resistant or developed resistance to third-generation EGFR inhibitors and show that ERBB2 and MET activation can confer resistance to these compounds. Furthermore, we identified a KRASG12S mutation in a patient with acquired resistance to AZD9291 as a potential driver of acquired resistance. Finally, we show that dual inhibition of EGFR/MEK might be a viable strategy to overcome resistance in EGFR-mutant cells expressing mutant KRAS. Conclusions: Our data suggest that heterogeneous mechanisms of resistance can drive primary and acquired resistance to third-generation EGFR inhibitors and provide a rationale for potential combination strategies. Clin Cancer Res; 22(19); 4837–47. ©2016 AACR.

Nitrated and Oxidized Plasma Proteins in Smokers and Lung Cancer Patients

Abstract: Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke). The levels of nitrated proteins were significantly higher in lung cancer patients than in controls (P = 0.003). On the other hand, the levels of oxidized proteins were significantly higher in smokers than in nonsmokers (P < 0.001). Western-blot analyses showed the presence of two to five nitrated proteins and one oxidized protein. Using immunoprecipitation and Western-blot analyses with eight different antibodies against human plasma proteins, we identified fibrinogen, transferrin, plasminogen, and ceruloplasmin as nitrated proteins and fibrinogen as the only oxidized protein present in human plasma of lung cancer patients and smokers. Our results indicate that cigarette smoking increases oxidative stress and that during lung cancer development, formation of reactive nitrogen species results in nitration and oxidation of plasma proteins.

Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models

Abstract: Summary Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RR prev ) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RR prev of HPV 16 among women and men was 0·53 (80% UI 0·46–0·68) and 0·36 (0·28–0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RR prev of HPV 16 among women and men was 0·93 (0·90–1·00) and 0·83 (0·75–1·00), respectively. Vaccinating boys in addition to girls increased the RR prev of HPV 16 among women and men by 0·18 (0·13–0·32) and 0·35 (0·27–0·39) for 40% coverage, and 0·07 (0·00–0·10) and 0·16 (0·01–0·25) for 80% coverage, respectively. The RR prev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RR prev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. Funding Canadian Institutes of Health Research.

Screening for cancer in low- and middle-income countries.

Abstract: Background Screening programs involve testing asymptomatic individuals with an accurate screening test to identify those likely to have the disease of interest and to further investigate them to confirm or exclude the disease. The aim of cancer screening is to prevent cancer deaths and improve quality of life by finding cancers early and by effectively treating them. A decision to introduce a screening program in public health services depends on the evidence that the benefits outweigh the harms of screening, disease burden, availability of suitable screening test, effective treatment, adequate resources, and efficient health services. Screening programs should achieve high participation for testing, diagnosis, and treatment to be effective and efficient. Objective To describe the current status of cancer screening programs in low- and middle-income countries (LMICs). Method A review of literature and on-going cancer screening initiatives in LMICs was made to discuss cancer screening in these countries. Findings Although population-based programs offering Papanicolaou testing every 3 to 5 years have reduced cervical cancer incidence and mortality in high-income countries, such programs have been less successful in reducing cervical cancer burden in LMICs due to poor organization, lack of coverage, and lack of quality assurance. The challenges in introducing high-quality cytology screening in LMICs have led to evaluation of alternative screening approaches such as visual inspection with acetic acid (VIA), human papillomavirus (HPV) testing-based screening, and novel paradigms such as a “single-visit screen and treat” in which treatment with cryotherapy or cold coagulation is provided to screen-positive women without clinical evidence of cancer. Both HPV testing and VIA have been found to prevent cervical neoplasia and cervical cancer deaths in clinical trials. Although mammography screening reduces breast cancer mortality, associated overdiagnosis and overtreatment and the balance between benefits and harms have received much attention in recent years. Although introduction of clinical breast examination screening in LMICs should wait for evidence from ongoing trials, improving breast awareness and access to early diagnosis and treatment in health services is a valuable breast cancer control option in LMICs. Organized colorectal cancer screening programs are still evolving and are in early stages of development in many high-income countries. To date, there is insufficient evidence to support the introduction of population-based stomach, lung, ovarian, and prostate cancer screening in public health services. Conclusions Implementation of VIA screening in several LMICs is conducive to future HPV screening programs when affordable HPV tests become widely available. Both HPV vaccination and HPV screening have a huge potential to eliminate cervical cancer in LMICs. A mammography screening program is a complex undertaking involving substantial resources and infrastructure that may not be feasible in many LMICs.