Epidermal growth factor receptor (EGFR) is a critical target in the treatment of nonsmall cell lung cancer (NSCLC). The mutations involving EGFR are more prevalent in patients of Asian ancestry, women, never smokers, and those with adenocarcinoma histology. Primary mechanism of resistance to EGFR-TKIs includes in frame insertion mutation in exon 20, de novo T790M mutation also on exon 20, activating mutations in KRAS, loss of PTEN, and amplification of c-MET whereas acquired resistance results from development of secondary alteration in ATP domain of T790M. There are many novel targeting agents in development to overcome resistance to EGFR TKIs.
Biomarkers to identify subjects at high-risk for developing lung cancer will revolutionize the disease outlook. Most biomarker studies have focused on patients already diagnosed with lung cancer and in most cases the disease is often advanced and incurable. The objective of this study was to use proteomics to identify a plasma biomarker for early detection of lung lesions that may subsequently be the harbinger for cancer. Plasma samples were obtained from subjects without lung cancer grouped as never, current, or ex-smokers. An iTRAQ-based proteomic analysis was performed on these pooled plasma samples. We identified 31 proteins differentially abundant in current smokers or ex-smokers relative to never smokers. Western blot and ELISA analyses confirmed the iTRAQ results that demonstrated an increase of apolipoprotein E (APOE) in current smokers as compared to both never and ex-smokers. There was a strong and significant correlation of the plasma APOE levels with development of premalignant squamous metaplasia. Additionally, we also showed that higher tissue levels of APOE are seen with squamous metaplasia, supporting a direct relationship. Our analysis reveals that elevated plasma APOE is associated with smoking, and APOE is a novel predictive protein biomarker for early morphological changes of squamous metaplasia in the lung.
Non-small cell lung cancer represents a group of heterogeneous diseases. The last decade witnessed significant progress in improving our understanding of the biology of non-small cell lung cancer, which led to the identification of several genetic targets. Those genetic targets were utilized to explain clinical phenomena, such as the occurrence of non-small cell lung cancer in never-smokers, to predict response to conventional chemotherapy and biological agents, and to explain and predict resistance to therapy. The progress in the treatment of non-small cell lung cancer in the last few years was based on a new generation of population-enriched clinical trials that utilized genetic targets such as somatic EGFR mutations and ALK-EML4 mutations. In this review we will discuss the available information about the key genetic markers of non-small cell lung cancer and the pivotal clinical trials that validate the use of those genetic markers in non-small cell lung cancer patients.
tory state associated with obesity, hyperinsulinemia, excess of insulin-like growth factor-1 (IGF-1), and altered metabolism of steroid hormones [ 5 ] . In MM, large meta-analyses of epidemiologic studies from analyzing associations between this cancer and body weight concluded that obesity is a risk factor for MM [ 3 , 6 , 7 ] . The most recent and comprehensive meta-analysis included 15 prospective cohort studies from various areas of the world, with relative risk (RR) estimates for the association between body mass index (BMI) and MM incidence or mortality. It concluded that the risk of MM is signifi cantly elevated among obese patients, with a RR of 1.21 (95 % CI, 1.08-1.35), and that the RR of MM mortality in these patients was 1.54 (95 % CI, 1.35-1.76) [ 6 ] . The hypothesis that obesity is a risk factor for MM has also been supported by the association between excess body weight and increased risk of monoclonal gammopathy of undetermined signifi cance (MGUS), the precursor state of MM [ 8 ] . It has been proposed that the excess risk of MM among obese patients could be related to the production of interleukin-6 (IL-6) Introduction ▼ Multiple myeloma (MM) is a rare cancer, because it represents 1 % of all malignancies. Its annual incidence is approximately 5/100 000 [ 1 ] . Little is known regarding the body weight status of MM patients both at diagnosis and during the course of the disease. In particular, it is unclear whether the current epidemic of obesity aff ects even MM patients, or, instead, they develop progressive weight loss and cachexia during the terminal phase of their disease. Excess body weight is a well-known risk factor not only for diabetes mellitus and cardiovascular disease, but even for cancer [ 2 , 3 ] . In fact, epidemiological evidence indicates that approximately 20 % of all cancers are related to excess body weight [ 4 ] , including 20 % of breast and colon cancer cases, and about 40 % of kidney and endometrial cancer cases [ 5 ] . Biologic mechanisms underlying the association between excess weight and cancer have not been completely elucidated, but several processes have been involved, including the presence of a chronic proinfl ammaAbstract ▼ Background: Little is known regarding body weight changes in patients with multiple myeloma (MM) during the course of their disease, and the infl uence of obesity in the overall survival (OS) of patients aff ected by this cancer. Methods: We retrospectively collected clinical data from 318 MM patients, and analyzed their weight and body mass index (BMI) at various points throughout the course of the disease, including baseline, pre-and post-peripheral blood stem cell transplant (PBSCT), and time of death. Results: At the time of diagnosis, median BMI was 28.1 ( ± 5.7 SD; range, 15.3-51.8). The majority of MM patients were either overweight or
Acute myelogenous leukemia (AML) is characterized by uncontrolled proliferation of the cells of myeloid origin. It can present at all ages, but is more common in adults. It is one of the most common leukemias in adults and continues to pose significant challenge in diagnosis and long-term management.AML is a disease at the forefront of genetic and genomic approaches to medicine. It is a disease that has witnessed rapid advances in terms of diagnosis, classification, prognosis and ultimately individualized therapy. Newly diagnosed AML patients are now routinely stratified according to cytogenetics and molecular markers which guides long-term prognosis and treatment. On the other hand, with few exceptions, the initial treatment (also known as induction treatment) of AML has been 'one-size-fits-all'. It remains a great challenge for patients and physicians to consolidate and translate these advances into eventual success in clinic [1, 2].
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