Lung cancer is a severe challenge to the health care system with intrinsic resistance to first and second-line chemo/radiotherapies. In view of the sterile environment of lung cancer, several immunotherapeutic drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are currently being used in clinics globally with the intention of releasing exhausted T-cells back against refractory tumor cells. Immunotherapies have a limited response rate and may cause immune-related adverse events (irAEs) in some patients. Hence, a deeper understanding of regulating immune checkpoint interactions could significantly enhance lung cancer treatments. In this review, we explore the role of miRNAs in modulating immunogenic responses against tumors. We discuss various aspects of how manipulating these checkpoints can bias the immune system’s response against lung cancer. Specifically, we examine how altering the miRNA profile can impact the activity of various immune checkpoint inhibitors, focusing on the PD-1/PD-L1 pathway within the complex landscape of lung cancer. We believe that a clear understanding of the host’s miRNA profile can influence the efficacy of checkpoint inhibitors and significantly contribute to existing immunotherapies for lung cancer patients. Additionally, we discuss ongoing clinical trials involving immunotherapeutic drugs, both as standalone treatments and in combination with other therapies, intending to advance the development of immunotherapy for lung cancer.

Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, β-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment–delivery mechanisms.

Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/β-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/β-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients.

The widespread public health problem of esophageal squamous cell carcinoma (ESCC) is the cause of an increasing number of deaths each year due to delayed diagnosis. Therefore, we require specific and sensitive new biomarkers to manage ESCC better. The detection of diseases, such as cancer, can now be achieved through non-invasive circulating blood-based methods. Blood-based circulating non-coding RNAs, such as miRNA and lncRNA, have been extensively used as valuable markers for lung, esophageal, and breast cancer diagnostic purposes, as quoted in our previous research. Herein, we investigated the role of novel long non-coding RNA EWSAT1 as a blood-based liquid biopsy biomarker for the ESCC. Our findings indicate that EWSAT1 lncRNA has an increased tumor suppressive activity in ESCC, as it reduces by ∼2.59-fold relative to healthy controls. Moreover, we established that EWSAT1 expression can significantly distinguish between clinicopathological characteristics, including age, gender, and lifestyle choices such as smoking, alcohol consumption, and drinking hot beverages among patients with ESCC and healthy individuals. In addition, the expression levels of lncRNA EWSAT1 could distinguish between individuals with more advanced ESCC cancer and those without it, as illustrated by the ROC curve (AUC = 0.7174, 95 % confidence intervals = 0.5901 to 0.8448, p-value = 0.001). Our in-silico prediction methods demonstrated that miR-873-5p is the direct target of EWSAT1, which competes with the tumor suppressor candidate 3 (TUSC3) and EGL-9 family hypoxia-inducible factor 3 (EGLN3) mRNAs through a sponging mechanism, creating the EWSAT1/miR-873-5p/mRNA axis. We have analyzed the role of EWSAT1 in various cellular processes and signaling pathways, including mTOR, Wnt, and MAPK signaling pathways. Circulating EWSAT1 can be used as a liquid biopsy marker for diagnosis of ESCC and has the potential to serve as an effective therapeutic biomarker, according to this pilot study.