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Lung adenocarcinoma is the most prevalent form of lung cancer, and drug resistance poses a significant obstacle in its treatment. This study aimed to investigate the overexpression of long non-coding RNAs (lncRNAs) as a mechanism that promotes intrinsic resistance in tumor cells from the onset of treatment. Drug-tolerant persister (DTP) cells are a subset of cancer cells that survive and proliferate after exposure to therapeutic drugs, making them an essential object of study in cancer treatment. The molecular mechanisms underlying DTP cell survival are not fully understood; however, long non-coding RNAs (lncRNAs) have been proposed to play a crucial role. DTP cells from lung adenocarcinoma cell lines were obtained after single exposure to tyrosine kinase inhibitors (TKIs; erlotinib or osimertinib). After establishing DTP cells, RNA sequencing was performed to investigate the differential expression of the lncRNAs. Some lncRNAs and one mRNA were overexpressed in DTP cells. The clinical relevance of lncRNAs was evaluated in a cohort of patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). RT-qPCR validated the overexpression of lncRNAs and mRNA in the residual DTP cells and LUAD biopsies. Knockdown of these lncRNAs increases the sensitivity of DTP cells to therapeutic drugs. This study provides an opportunity to investigate the involvement of lncRNAs in the genetic and epigenetic mechanisms that underlie intrinsic resistance. The identified lncRNAs and CD74 mRNA may serve as potential prognostic markers or therapeutic targets to improve the overall survival (OS) of patients with lung cancer.

Over a century ago, bacterial extracts were found to be useful in cancer therapy, but this treatment modality was obviated for decades. Currently, in spite of the development and advances in chemotherapies and radiotherapy, failure of these conventional treatments still represents a major issue in the complete eradication of tumor cells and has led to renewed approaches with bacteria-based tumor therapy as an alternative treatment. In this context, live-attenuated bacteria, particularly Salmonella enterica , have demonstrated tumor selectivity, intrinsic oncolytic activity, and the ability to induce innate or specific antitumor immune responses. Moreover, Salmonella enterica also has strong potential as a delivery system of tumor-associated antigens, cytotoxic molecules, immunomodulatory molecules, pro-apoptotic proteins, and nucleic acids into eukaryotic cells, in a process known as bactofection and antitumor nanoparticles. In this review, we present the state of the art of current preclinical and clinical research on the use of Salmonella enterica as a potential therapeutic ally in the war against cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.