Search

The JADE family comprises three members encoded by individual genes and roles for these proteins have been identified in chromatin remodeling, cell cycle progression, cell regeneration and the DNA damage response. JADE family members, and in particular JADE2 have not been studied in any great detail in cancer. Using a series of standard biological and bioinformatics approaches we investigated JADE2 expression in surgically resected non-small cell lung cancer (NSCLC) for both mRNA and protein to examine for correlations between JADE2 expression and overall survival. Additional correlations were identified using bioinformatic analyses on multiple online datasets. Our analysis demonstrates that JADE2 expression is significantly altered in NSCLC. High expression of JADE2 is associated with a better 5-year overall survival. Links between JADE2 mRNA expression and a number of mutated genes were identified, and associations between JADE2 expression and tumor mutational burden and immune cell infiltration were explored. Potential new drugs that can target JADE2 were identified. The results of this biomarker-driven study suggest that JADE2 may have potential clinical utility in the diagnosis, prognosis and stratification of patients into various therapeutically targetable options. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related mortality in the developed world. The majority of patients with non-small cell lung cancer (NSCLC) present with advanced disease. Even in the one-third of patients presenting with early-stage disease, there is a high rate of relapse despite complete surgical resection. As most patients recur with distant metastases, it is hypothesized that micrometastases may be present at the time of surgery, suggesting a potential role for adjuvant chemotherapy. Postoperative cisplatin-based chemotherapy has been established as the standard of care in resected stage II-III NSCLC, improving 5-year survival by 8-15%. This review explores the evolution of adjuvant chemotherapy trials since the 1970s, charts what progress has been made to date, and analyzes the evidence leading to current standards of care. We also review some of the retrospective studies evaluating potential biomarkers in NSCLC and evaluate whether these may contribute to the heterogeneity of the chemotherapy response and assist in tailoring treatment. In addition, we review current studies of targeted therapy in the adjuvant setting and offer potential future directions for research. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide. While partial or complete tumor regression can be achieved in patients, particularly with cisplatin-based strategies, these initial responses are frequently short-lived and are followed by tumor relapse and chemoresistance. Identifying the root of cisplatin resistance in NSCLC and elucidating the mechanism(s) of tumor relapse, is of critical importance in order to determine the point of therapeutic failure, which in turn, will aid the discovery of novel therapeutics, new combination strategies and a strategy to enhance the efficacy of current chemotherapeutics. It has been hypothesized that cancer stem cells (CSCs) may be the initiating factor of resistance. We have previously identified and characterized an aldehyde dehydrogenase 1 CSC subpopulation in cisplatin resistant NSCLC. BBI608 is a small molecule STAT3 inhibitor known to suppress cancer relapse, progression and metastasis. Here, we show that BBI608 can inhibit stemness gene expression, deplete CSCs and overcome cisplatin resistance in NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Lung cancer is a leading cause of cancer-related mortality in North America. In addition to tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether genetic sequence variants (GSVs) associated with lung cancer risk are associated with overall survival (OS) and progression-free survival (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients. Methods: A total of 20 candidate GSVs in 12 genes previously reported to be associated with lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC. Multivariate Cox proportional hazard models adjusted for potential clinical prognostic factors were generated for OS and PFS. Results: After taking into account multiple comparisons, one GSV remained significant: rs4975616 on chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio (aHR) for OS was 0.75 (0.69–0.91), p =0.002; for PFS aHR was 0.74 (0.62–0.89), p <0.001 for each protective variant allele. Results were similar in both Stage III (OS: aHR=0.70; PFS: aHR=0.71) and Stage IV patients (OS: aHR=0.81; PFS: aHR=0.77). Conclusion: A GSV on 5p15.33 is not only a risk factor for lung cancer but may also be associated with survival in patients with late stage NSCLC. If validated, GSVs may define subsets of patients with different risk and prognosis of NSCLC. [Copyright &y& Elsevier]