DNA methylation, an epigenetic modification, regulates gene transcription and maintains genome stability. DNA methyltransferase (DNMT) inhibitors can activate silenced genes at low doses and cause cytotoxicity at high doses. The ability of DNMT inhibitors to reverse epimutations is the basis of their use in novel strategies for cancer therapy. In this review, we examined the literature on DNA methyltransferase inhibitors. We summarized the mechanisms underlying combination therapy using DNMT inhibitors and clinical trials based on combining hypomethylation agents with other chemotherapeutic drugs. We also discussed the efficacy of such compounds as antitumor agents, the need to optimize treatment schedules and the regimens for maximal biologic effectiveness. Notably, the combination of DNMT inhibitors and chemotherapy and/or immune checkpoint inhibitors may provide helpful insights into the development of efficient therapeutic approaches.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet

Watson for Oncology (WFO) is a artificial intelligence clinical decision-support system with evidence-based treatment options for oncologists. WFO has been gradually used in China, but limited reports on whether WFO is suitable for Chinese patients. This study aims to investigate the concordance of treatment options between WFO and real clinical practice for Cervical cancer patients retrospectively. We retrospectively enrolled 300 cases of cervical cancer patients. WFO provides treatment options for 246 supported cases. Real clinical practice were defined as concordant if treatment options were designated “recommended” or “for consideration” by WFO. Concordance of treatment option between WFO and real clinical practice was analyzed statistically. The treatment concordance between WFO and real clinical practice occurred in 72.8% (179/246) of cervical cancer cases. Logistic regression analysis showed that rural registration residences, advanced age, poor ECOG performance status, stages II-IV disease have a remarkable impact on consistency. The main reasons attributed to the 27.2% (67/246) of the discordant cases were the substitution of nedaplatin for cisplatin, reimbursement plan of bevacizumab, surgical preference, and absence of neoadjuvant/adjuvant chemotherapy and PD-1/PD-L1 antibodies recommendations. WFO recommendations were in 72.8% of concordant with real clinical practice for cervical cancer patients in China. However, several localization and individual factors limit its wider application. So, WFO could be an essential tool but it cannot currently replace oncologists. To be rapidly and fully apply to cervical cancer patients in China, accelerate localization and improvement were needed for WFO.

With the widespread implementation of lung cancer screening, more and more patients are being diagnosed with multiple primary lung cancers (MPLCs). In the era of precision medicine, many controversies remain in differentiating MPLCs from intrapulmonary metastasis and the optimum treatment choice, especially in patients exhibiting similar histology. In this review, we summarize common diagnostic criteria and novel discrimination methods with a special emphasis on the emerging value of broad panel next-generation sequencing (NGS) for the diagnosis of MPLCs. We then discuss current advances regarding therapeutic approaches for MPLCs. Radical surgery is the main treatment modality, while stereotactic body radiotherapy (SBRT) is safe and feasible for early-stage MPLC patients with inoperable tumors. In addition, immunotherapy and targeted therapy, particularly epidermal growth factor receptor-tyrosine kinase inhibitors, are emerging therapeutic strategies that are still in their infancy. Characteristics of both genomic profiles and tumor microenvironment are currently being evaluated but warrant further exploration to facilitate the application of targeted systematic therapies in MPLC patients.

Background: Systemic inflammation response index (SIRI) has been reported to be an effective blood-based biomarker for predicting prognosis in various kinds of cancer patients. However, the prognostic role of SIRI in advanced lung adenocarcinoma patient remains unclear. Methods: The aim of the present study is to evaluate the prognostic role of SIRI in EGFR-mutant advanced lung adenocarcinoma patients treated with first-generation EGFR-TKIs. A total of 245 patients who received gefitinib, erlotinib, or icotinib at the Second Xiangya Hospital were retrospectively evaluated. SIRI was defined as neutrophil count×monocyte/lymphocyte count. The optimal cut-off value was determined according to receiver operation characteristic curve analysis. Characteristics of patients were compared via chi-square test or Fisher’s exact test. Survivals were estimated by the Kaplan–Meier method and compared by the Log rank test. Multivariate analysis was estimated using the Cox proportional hazards model. Results: It is showed that high SIRI was associated with male patient, smoker, worse ECOG PS, 19-DEL mutation. Kaplan–Meier survival analysis showed that ECOG PS, brain metastasis, SIRI were significantly correlated with progression-free survival (PFS), and gender, ECOG PS, brain metastasis, NLR and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI and ECOG PS independently predict PFS and OS. Conclusion: Our findings indicate that SIRI is an effective and convenient marker for predicting prognosis in advanced EGFR-mutant lung adenocarcinoma patients treated with first-generation TKI.