Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug delivery systems, enabling targeted delivery of therapeutic agents to cancer cells while minimizing off-target effects and reducing systemic toxicity. In the context of OC, the integration of aptamers with non-coding RNAs (ncRNAs) presents an opportunity for precise and efficient gene targeting. Additionally, the conjugation of aptamers with nanoparticles allows for accurate and targeted delivery of ncRNAs to specific cells, tissues, or organs. In this review, we will summarize the potential use and challenges associated with the use of aptamers alone or aptamer–ncRNA conjugates, nanoparticles, and multivalent aptamer-based therapeutics for the treatment of OC.

A series of new ursolic acid (UA) derivatives substituted with various amino acids (AAs) or dipeptides (DP) at the C-3 position of the steroid skeleton was designed and synthesized. The compounds were obtained by the esterification of UA with the corresponding AAs. The cytotoxic activity of the synthesized conjugates was determined using the hormone-dependent breast cancer cell line MCF-7 and the triple-negative breast cancer cell line MDA. Three derivatives (l-seryloxy-, l-prolyloxy- and l-alanyl-l-isoleucyloxy-) showed micromolar IC₅₀ values and reduced the concentrations of matrix metalloproteinases 2 and 9. Further studies revealed that for two compounds (l-seryloxy- and l-alanyl-l-isoleucyloxy-), a possible mechanism of their antiproliferative action is the activation of caspase-7 and the proapoptotic Bax protein in the apoptotic pathway. The third compound (l-prolyloxy- derivative) showed a different mechanism of action as it induced autophagy as measured by an increase in the concentrations of three autophagy markers: LC3A, LC3B, and beclin-1. This derivative also showed statistically significant inhibition of the proinflammatory cytokines TNF-α and IL-6. Finally, for all synthesized compounds, we computationally predicted their ADME properties as well as performed molecular docking to the estrogen receptor to assess their potential for further development as anticancer agents.

Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1—were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells.

Mucin 1 (MUC1) is a high molecular weight transmembrane glycoprotein, that is overexpressed in >90% of breast cancers. It serves a crucial role in anti‑apoptosis and tumor progression. MUC1 interacts with proteins in the extracellular matrix, at the cell membrane, in the cytoplasm and in the nucleus. The aim of the present study was to investigate the mechanism of anticancer action induced by novel berenil complex of platinum(II) (Pt12) together with a monoclonal antibody against MUC1 in breast cancer MCF‑7 cells. The effect of combined treatment on the concentration of selected markers of apoptosis including proapoptotic B‑cell lymphoma 2 associated X protein (Bax), caspase‑8, cytochrome c and caspase‑9, as well as selected proteins involved in intracellular signal transduction pathways including p53, phosphoinositide 3‑kinase and phosphorylated protein kinase B (p‑Akt) were analyzed. The results of the present study demonstrated that combined treatment may be a promising strategy in anticancer treatment and represents an alternative to monotherapy. All compounds used alone (Pt12, cisplatin and the anti‑MUC1 antibody) increased the concentration of proapoptotic Bax, cytochrome c and caspase‑9 in comparison with control, thus suggesting that they activated the mitochondrial apoptotic pathway. Pt12 alone significantly increased the concentration of caspase‑8, which is responsible for the initiation of the extrinsic apoptotic pathway. However, the strongest effect was observed following Pt12 (20 µM) treatment combined with the anti‑MUC1 antibody (10 µg/ml). These two compounds together strongly induced apoptosis in MCF‑7 breast cancer cells via the external and internal apoptotic pathways. It was also demonstrated that combined treatment based on Pt12 and the anti‑MUC1 antibody significantly reduced p-Akt concentration.

Many studies have shown that naturally occurring compounds may support prevention and treatment of various diseases, including cancer. Pharmacological investigations revealed a wide spectrum of Nigella sativa biological activities. Combining natural compounds together with synthetic drugs may increase the anticancer activity and limit severe side effects of such a treatment and may be an alternative to monotherapy. The aim of the study was to evaluate the cytotoxic and proapoptotic effects of a novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative and its effect in combination with Nigella sativa seed oil or extract in human gastric cancer cells (AGS). Etoposide was used as a reference. Our studies proved that combination strategy based on novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivative (OM-90) with Nigella sativa seed oil or extract represents the strongest efficacy in AGS cancer cells as compared to monotherapy and combined treatment with Nigella sativa seed oil or extract together with etoposide. Such a combination also leads to the activation of mitochondrial pathway, which plays a significant role in molecular mechanism of induction of apoptosis by these compounds.

The aim of the present study was to examine the multi-targeted potential of a monoclonal antibody against mucin-1 (MUC1) and novel octahydropyrazin[2,1-a:5,4-a ']diisoquinoline derivative (OM-86II) in estrogen receptor-positive MCF-7 human breast cancer cells. The cell viability was measured by an MTT assay. The analyses of cell cycle and disruption of mitochondrial membrane potential were performed by flow cytometry. Fluorescent microscopy and flow cytometry were used to demonstrate the effect of the compounds on apoptosis. ELISA was conducted to check the concentrations of proteins involved in multiple intracellular signaling pathways, responsible for the promotion of tumor growth and breast cancer progression, namely matrix metalloproteinase (MMP)-2, matrix MMP-9, tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), soluble intercellular adhesion molecule 1 (sICAM1) and mTOR. The combination therapy based on anti-MUC1 antibody and novel OM-86II inhibited the proliferation of MCF-7 breast cancer cells. Its inhibitory effects were associated with the induction of cell cycle arrest and apoptosis. It was demonstrated that anti-MUC1 antibody with OM-86II decreased the concentrations of MMP-2, MMP-9, sICAM1 and mTOR. In addition, the combined therapy exhibited anti-inflammatory activity, which was demonstrated by a decrease in TNF-alpha and COX-2 concentrations. The present data provided evidence that the combination of anti-MUC1 antibody with novel OM-86II represents a multi-targeted strategy in MCF-7 breast cancer treatment.