Noncoding RNAs (ncRNAs) include a diverse range of RNA species, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs, ncRNAs of approximately 19–25 nucleotides in length, are involved in gene expression regulation either via degradation or silencing of the messenger RNAs (mRNAs) and have roles in multiple biological processes, including cell proliferation, differentiation, migration, angiogenesis, and apoptosis. LncRNAs, which are longer than 200 nucleotides, comprise one of the largest and most heterogeneous RNA families. LncRNAs can activate or repress gene expression through various mechanisms, acting alone or in combination with miRNAs and other molecules as part of various pathways. Until recently, most research has focused on individual lncRNA and miRNA functions as regulators, and there is limited available data on ncRNA interactions relating to the tumor growth, metastasis, and therapy of cancer, acting either on mRNA alone or as competing endogenous RNA (ceRNA) networks. Triple-negative breast cancer (TNBC) represents approximately 10%–20% of all breast cancers (BCs) and is highly heterogenous and more aggressive than other types of BC, for which current targeted treatment options include hormonotherapy, PARP inhibitors, and immunotherapy; however, no targeted therapies for TNBC are available, partly because of a lack of predictive biomarkers. With advances in proteomics, new evidence has emerged demonstrating the implications of dysregulation of ncRNAs in TNBC etiology. Here, we review the roles of lncRNAs and miRNAs implicated in TNBC, including their interactions and regulatory networks. Our synthesis provides insight into the mechanisms involved in TNBC progression and has potential to aid the discovery of new diagnostic and therapeutic strategies.

Oncolytic viruses (OVs) are emerging as potential treatment options for cancer. Natural and genetically engineered viruses exhibit various antitumor mechanisms. OVs act by direct cytolysis, the potentiation of the immune system through antigen release, and the activation of inflammatory responses or indirectly by interference with different types of elements in the tumor microenvironment, modification of energy metabolism in tumor cells, and antiangiogenic action. The action of OVs is pleiotropic, and they show varied interactions with the host and tumor cells. An important impediment in oncolytic virotherapy is the journey of the virus into the tumor cells and the possibility of its binding to different biological and nonbiological vectors. OVs have been demonstrated to eliminate cancer cells that are resistant to standard treatments in many clinical trials for various cancers (melanoma, lung, and hepatic); however, there are several elements of resistance to the action of viruses per se. Therefore, it is necessary to evaluate the combination of OVs with other standard treatment modalities, such as chemotherapy, immunotherapy, targeted therapies, and cellular therapies, to increase the response rate. This review provides a comprehensive update on OVs, their use in oncolytic virotherapy, and the future prospects of this therapy alongside the standard therapies currently used in cancer treatment.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The trifunctional antibody catumaxomab is a highly effective anti‐cancer therapeutic that is administered to patients suffering from malignant ascites intraperitoneally (i.p.) in microgram (µg) doses. So far, no clinical pharmacokinetic data are available. WHAT THIS STUDY ADDS • Catumaxomab attains effective local concentrations in the ascites fluid and shows low systemic exposure with an acceptable safety profile confirming the appropriateness of the i.p. application scheme.AIMS Catumaxomab is the first EMEA approved trifunctional anti‐EpCAM×anti‐CD3 antibody for the treatment of cancer patients with malignant ascites. A phase II pharmacokinetic study was conducted to determine local and systemic antibody concentrations and anti‐drug antibody (ADA) development.METHODS Thirteen cancer patients with symptomatic malignant ascites were treated with four ascending doses of 10, 20, 50, and 150 µg catumaxomab intraperitoneally (i.p.) infused on days 0, 3, 6 or 7 and 10. The pharmacokinetics of catumaxomab were studied by implementation of supportive data from a non clinical mouse tumour model. Additionally, ADA development was monitored.RESULTS Ten out of 13 patients were evaluable for pharmacokinetic analysis. Catumaxomab became increasingly concentrated in ascites during the course of treatment, attaining effective concentrations in the ng ml⁻¹ range. Catumaxomab remained immunologically active even after several days in the circulation. The observed systemic catumaxomab exposure was low (<1%), with a maximal median plasma concentration (C_max) of 403 pg ml⁻¹. The mean elimination half‐life in the plasma was 2.13 days. All patients developed ADA, but not before the last infusion. High observed inter‐individual variability and low systemic exposure may be explained by the inverse correlation between tumour burden, effector cell numbers and systemic antibody bioavailability as demonstrated in a defined mouse tumour model.CONCLUSIONS Based on the high and effective local concentrations, low systemic exposure and acceptable safety profile, we confirmed that the i.p. application scheme of catumaxomab for the treatment of malignant ascites is appropriate.

Objectives: Treatment decision-making in colorectal cancer is often guided by tumour tissue molecular analysis. The aim of this study was the development and validation of a high-resolution melting (HRM) method for the detection ofKRAS,NRASandBRAFmutations in Greek and Romanian patients with colorectal cancer and determination of the frequency of these mutations in the respective populations.Setting: Diagnostic molecular laboratory located in Athens, Greece.Participants: 2425 patients with colorectal cancer participated in the study.Primary and secondary outcome measures: 2071 patients with colorectal cancer (1699 of Greek and 372 of Romanian origin) were analysed forKRASexon 2 mutations. In addition, 354 tumours from consecutive patients (196 Greek and 161 Romanian) were subjected to fullKRAS(exons 2, 3 and 4),NRAS(exons 2, 3 and 4) andBRAF(exon 15) analysis.KRAS,NRASandBRAFmutation detection was performed by a newly designed HRM analysis protocol, followed by Sanger sequencing.Results: KRASexon 2 mutations (codons 12/13) were detected in 702 of the 1699 Greek patients with colorectal carcinoma analysed (41.3%) and in 39.2% (146/372) of the Romanian patients. Among the 354 patients who were subjected to fullKRAS,NRASandBRAFanalysis, 40.96% hadKRASexon 2 mutations (codons 12/13). Among theKRASexon 2 wild-type patients 15.31% harboured additionalRASmutations and 12.44%BRAFmutations. The newly designed HRM method used showed a higher sensitivity compared with the sequencing method.Conclusions: The HRM method developed was shown to be a reliable method forKRAS,NRASandBRAFmutation detection. Furthermore, no difference in the mutation frequency ofKRAS,NRASandBRAFwas observed between Greek and Romanian patients with colorectal cancer.

Cervical cancer represents a major health problem among females due to its increased mortality rate. The conventional therapies are very aggressive and unsatisfactory when it comes to survival rate, especially in terminal stages, which requires the development of new treatment alternatives. With the use of nanotechnology, various chemotherapeutic drugs can be transported via nanocarriers directly to cervical cancerous cells, thus skipping the hepatic first-pass effect and decreasing the rate of chemotherapy side effects. This review comprises various drug delivery systems that were applied in cervical cancer, such as lipid-based nanocarriers, polymeric and dendrimeric nanoparticles, carbon-based nanoparticles, metallic nanoparticles, inorganic nanoparticles, micellar nanocarriers, and protein and polysaccharide nanoparticles. Nanoparticles have a great therapeutic potential by increasing the pharmacological activity, drug solubility, and bioavailability. Through their mechanisms, they highly increase the toxicity in the targeted cervical tumor cells or tissues by linking to specific ligands. In addition, a nondifferentiable model is proposed through holographic implementation in the dynamics of drug delivery dynamics. As any hologram functions as a deep learning process, the artificial intelligence can be proposed as a new analyzing method in cervical cancer.