Compounds In Cancer Therapy Research Articles

Updated aspects of alpha-Solanine as a potential anticancer agent: Mechanistic insights and future directions.

Cancer remains a critical global health challenge, with limited progress in reducing mortality despite advancements in diagnosis and treatment. The growing resistance of tumors to existing chemotherapy exacerbates this burden. In response, the search for new anticancer compounds from plants has intensified, given their historical success in yielding effective treatments. This review focuses on α-solanine, a glycoalkaloid primarily derived from potato tubers and nightshade family plants, recognized for its diverse biological activities, including anti-allergic, antipyretic, anti-inflammatory, anti-diabetic, and antibiotic properties. Recently, α-solanine has gained attention as a potential anticancer agent. Utilizing resources like PubMed/MedLine, ScienceDirect, Web of Science, Scopus, the American Chemical Society, Google Scholar, Springer Link, Wiley, and various commercial websites, this review consolidates two decades of research on α-solanine's anticancer effects and mechanisms against nine different cancers, highlighting its role in modulating various signaling pathways. It also discusses α-solanine's potential as a lead compound in cancer therapy. The abundant availability of potato peel, often discarded as waste or sold cheaply, is suggested as a sustainable source for large-scale α-solanine extraction. The study concludes that α-solanine holds promise as a standalone or adjunctive cancer treatment. However, further research is necessary to optimize this lead compound and mitigate its toxicity through various strategies.

Comprehensive review of metal-based coordination compounds in cancer therapy: from design to biochemical reactivity

Abstract Throughout history, metal-based coordination compounds have been used for medical purposes, including the treatment of various illnesses like cancer. Since the discovery of cisplatin in 1965, many other metal coordinating complexes have been developed and evaluated, involving metals such as platinum, iron, zinc, ruthenium, gold, silver, titanium, and copper. The goal behind these efforts is to create effective and safe medications. At the moment, there are a lot of studies talking about the use of cytostatic metal complexes, mainly on promising platinum- and non-platinum-based drugs in both preclinical and clinical trials. However, there is a lack of recent comprehensive studies that cover both the chemical and biological aspects of metal-based coordinating molecules in the context of cancer therapy. This review aims to provide a thorough analysis of the coordination chemistry of existing and innovative cytostatic substances. It will include a description of their design and synthesis, as well as a summary of the biochemical reactivity and physicochemical features of potential metal-containing complexes.

Investigating Anti-cancer, Anti-oxidant and Immunomodulatory Effects of Essential Oils: Focusing on Oliveria Decumbens and Zataria Multiflora Essential Oils

Background: Cancer therapy necessitates innovative approaches with enhanced efficacy and reduced side effects. Essential oils have gained attention because of their diverse biological properties and relatively low toxicity. Zataria multiflora essential oil (ZEO) and Oliveria decumbens essential oil (OEO) exhibit promising anti-cancer effects, particularly in modifying oxidative stress and inflammation. Both oils boast complex compositions rich in bioactive compounds, including oxygenated monoterpenes and phenolic compounds like carvacrol and thymol. Hence, this study investigates essential oils’ anti-cancer, anti-oxidant and immunomodulatory effects, focusing on ZEO and OEO. Materials and Methods: This review briefly considers the intricate mechanisms of several essential oils, encompassing anti-oxidant, anti-inflammatory and anti-cancer properties. Then the review delves into the multifaceted mechanisms underlying the anti-cancer properties of ZEO and OEO. Results: Studies showcase the ability of ZEO and OEO to induce apoptosis in cancer cells through various pathways, such as mitochondrial dysfunction, reactive oxygen species (ROS) generation and DNA damage while sparing normal cells. Our studies further validated the immunomodulatory effects of OEO and ZEO in tumor-bearing mice, resulting in reduced tumor volume. Additionally, this review confirmed the synergistic effect of ZEO when combined with doxorubicin to inhibit cancer cells. Conclusion: Some essential oils, such as ZEO and OEO, present promising natural compounds in cancer therapy, offering diverse mechanisms of action targeting various aspects of tumor biology.

Enhancing anti-cancer capacity: Novel class I/II HDAC inhibitors modulate EMT, cell cycle, and apoptosis pathways

Cancer has been a leading cause of death over the last few decades in western countries as well as in Taiwan. However, traditional therapies are limited by the adverse effects of chemotherapy and radiotherapy, and tumor recurrence may occur. Therefore, it is critical to develop novel therapeutic drugs. In the field of HDAC inhibitor development, apart from the hydroxamic acid moiety, 2-aminobenzamide also functions as a zinc-binding domain, which is shown in well-known HDAC inhibitors such as Entinostat and Chidamide. With recent successful experiences in synthesizing 1-(phenylsulfonyl)indole-based compounds, in this study, we further combined two features of the above chemical compounds and generated indolyl benzamides. Compounds were screened in different cancer cell lines, and enzyme activity was examined to demonstrate their potential for anti-HDAC activity. Various biological functional assays evidenced that two of these compounds could suppress cancer growth and migration capacity, through regulating epithelial–mesenchymal transition (EMT), cell cycle, and apoptosis mechanisms. Data from 3D cancer cells and the in vivo zebrafish model suggested the potential of these compounds in cancer therapy in the future.

Antioxidant Activity and Antitumor Potential of Hedyotis chrysotricha Extract in Human Colorectal Cancer and Breast Cancer Cell Lines

Background: Cancer is a serious disease severely endangering human health and life in the world in the world, and conventional anticancer drugs have frequently suffered from severe side effects and resistance. Therefore, developing novel and effective therapeutic strategies is urgently needed. As a Chinese herbal medicine with important medical values, Hedyotis chrysotricha has been suggested to be useful for the treatment of many diseases, especially cancer. Objective: Our aim was to investigate the antioxidant and antitumor activities of the phytochemical extracts of H. chrysotricha. Methods: 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay was applied to determine antioxidant property. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay, wound healing assay, transwell matrix assay, flow cytometry and cell morphology were established to observe anti-proliferative, anti-migration, anti-invasion and apoptosis induction effects. The intracellular reactive oxygen species generation was detected by reactive oxygen species detection assay. Results: The ethyl acetate fraction showed promising antioxidant activity with IC50 of 98.67±0.49 μg/ml, and petroleum ether fraction exhibited the most potent antiproliferative effect on various human cancer cell lines, especially MDA-MB-231 (IC50 = 8.90±1.23 μg/ml) and HCT-116 (IC50 = 9.69±3.69 μg/ml) cancer cells. Further investigation revealed that the petroleum ether fraction suppressed the proliferation, migration and invasion of the cancer cells significantly. Additionally, it promoted cell apoptosis by increasing reactive oxygen species levels. Conclusion: H. chrysotricha extract possessed excellent antioxidant and antitumor activities. Therefore, it could be useful as a source of antioxidants and compounds for cancer therapy.

Emerging tendencies for the nano-delivery of gambogic acid: a promising approach in oncotherapy.

Despite the advancements in cancer therapies during the past few years, chemo/photo resistance, severe toxic effects, recurrence of metastatic tumors, and non-selective targeting remain incomprehensible. Thus, much effort has been spent exploring natural anticancer compounds endowed with biosafety and high effectiveness in cancer prevention and therapy. Gambogic acid (GA) is a promising natural compound in cancer therapy. It is the major xanthone component of the dry resin extracted from the Garcinia hanburyi Hook. f. tree. GA has significant antiproliferative effects on different types of cancer, and it exerts its anticancer activities through various pathways. Nonetheless, the clinical translation of GA has been hampered, partly due to its water insolubility, low bioavailability, poor pharmacokinetics, rapid plasma clearance, early degradation in blood circulation, and detrimental vascular irritation. Lately, procedures have been invented demonstrating the ability of nanoparticles to overcome the challenges associated with the clinical use of natural compounds both in vitro and in vivo. This review sheds light on the recent emerging trends for the nanodelivery of GA to cancer cells. To the best of our knowledge, no similar recent review described the different nanoformulations designed to improve the anticancer therapeutic activity and targeting ability of GA.

Organometallic Osmium Compounds in Cancer Therapy

Organometallic Osmium Compounds in Cancer Therapy

Natural compounds modulating mitophagy: Implications for cancer therapy

Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden. Although chemotherapy is the most widely used treatment for cancer, its effectiveness is limited by drug resistance and severe side effects. Mitophagy is the principal mechanism that degrades damaged mitochondria via the autophagy/lysosome pathway to maintain mitochondrial homeostasis. Emerging evidence indicates that mitophagy plays crucial roles in tumorigenesis, particularly in cancer therapy. Mitophagy can exhibit dual effects in cancer, with both cancer-inhibiting or cancer-promoting function in a context-dependent manner. A variety of natural compounds have been found to affect cancer cell death and display anticancer properties by modulating mitophagy. In this review, we provide a systematic overview of mitophagy signaling pathways, and examine recent advances in the utilization of natural compounds for cancer therapy through the modulation of mitophagy. Furthermore, we address the inquiries and challenges associated with ongoing investigations concerning the application of natural compounds in cancer therapy based on mitophagy. Overcoming these limitations will provide opportunities to develop novel interventional strategies for cancer treatment.

Wireframe DNA Origami for the Cellular Delivery of Platinum(II)-Based Drugs

The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size, addressability, nontoxicity, and capacity to carry bioactive molecules, are promising vehicles for therapeutic delivery. Different approaches have been developed for manipulating and folding DNA origami, resulting in compact lattice-based and wireframe designs. Platinum-based complexes, such as cisplatin and phenanthriplatin, have gained attention for their potential in cancer and antiviral treatments. Phenanthriplatin, in particular, has shown significant antitumor properties by binding to DNA at a single site and inhibiting transcription. The present work aims to study wireframe DNA origami nanostructures as possible carriers for platinum compounds in cancer therapy, employing both cisplatin and phenanthriplatin as model compounds. This research explores the assembly, platinum loading capacity, stability, and modulation of cytotoxicity in cancer cell lines. The findings indicate that nanomolar quantities of the ball-like origami nanostructure, obtained in the presence of phenanthriplatin and therefore loaded with that specific drug, reduced cell viability in MCF-7 (cisplatin-resistant breast adenocarcinoma cell line) to 33%, while being ineffective on the other tested cancer cell lines. The overall results provide valuable insights into using wireframe DNA origami as a highly stable possible carrier of Pt species for very long time-release purposes.

Inorganic Compounds Utilized in Cancer Therapy: A Comprehensive Review

Background: Cancer is the most feared disease, with more than 1.6 million cases yearly. Cancer can start almost anywhere in the human body, from the uncontrollable growth and multiplication of damaged cells. Cancerous tumors can spread into the human body (a process called metastasis) in a solid form usually, but the cancers of the blood generally do not. Methods: The review analyzes a wide range of scientific literature and research studies to assess the efficacy and mechanisms of action of different inorganic compounds in cancer therapy. It covers both preclinical and clinical studies, examining the effects of these compounds on tumor growth inhibition, apoptosis induction, and modulation of signaling pathways. Results: Cancer treatment includes chemotherapy, surgery, and radiation. In this article, we will address inorganic compounds as a source of treatment, diagnosis, and carriers of active substances. Overall, this comprehensive review highlights the diverse roles of inorganic compounds in cancer therapy. It emphasizes the importance of further research to better understand the mechanisms of action, optimize dosage regimens, and enhance the clinical efficacy of these compounds in the treatment of cancer. Conclusion: The findings presented in this review contribute to the development of innovative and effective therapeutic strategies for cancer treatment. Keywords: cancer; cisplatin; selenium; zinc; copper; gold

Exploring the potential of chromone scaffold compounds in cancer therapy: targeting key kinase pathways

Exploring the potential of chromone scaffold compounds in cancer therapy: targeting key kinase pathways

Synthesis, Molecular Dynamics Simulation, and In-vitro Antitumor Activity of Quinazoline-2,4,6-triamine Derivatives as Novel EGFR Tyrosine Kinase Inhibitors.

Developing a potent and safe scaffold is challenging in anti-cancer drug discovery. The study focused on developing novel series of compounds based on the inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) as one of the most promising compounds in cancer therapy. In this study, a novel series of quinazoline-2,4,6-triamine derivatives were designed and synthesized through intramolecular C-H activation reaction of para-nitro aniline, trichloroacetonitrile, and isocyanides employing a one-pot reaction. The in-vitro antitumor activities of the compounds which showed acceptable inhibitory effects were investigated against breast (MCF-7), lung (A-549), and colon (HT-29) cancer cell lines by employing MTT assay. All compounds had the most negligible cytotoxicity toward normal fibroblast human cell lines. Based on structural and thermodynamics analysis results, it was found that Met 769 is a key residue in interaction with all inhibitors through the formation of hydrogen bonds with high occupancies with the amine group on the quinazoline ring of inhibitors. Also, there was a good consistency between calculated ΔG binding and experimental IC50 values of compounds 10d, 10e, and erlotinib. Compound 10e had an extensive range of antitumor activity on three diverse cell lines comparable with erlotinib and doxorubicin reference drugs. Also, compound 10d showed selective cytotoxicity against cancerous lung cells (A-549). On the other side, computational studies confirmed that Met 769 is a crucial residue in interaction with all inhibitors.

Exopolysaccharides of Fungal Origin: Properties and Pharmaceutical Applications

Fungal exopolysaccharides (EPSs) represent an important group of bioactive compounds secreted by fungi. These biopolymers can be utilized individually or in combination with different bioactive substances for a broad range of pharmaceutical field applications, due to their various biological activities, such as antioxidant, antimicrobial, anti-inflammatory, antiviral, anti-diabetic, and anticoagulant effects. The paper presents an up-to-date review of the main fungal polysaccharides (pullulan, schizophyllan, scleroglucan, botryosphaeran, lentinan, grifolan, and lasiodiplodan), highlighting their structures, producing strains, and useful properties in a double position, as controlled release (rate and selectively targeting) drug carriers, but mostly as active immunomodulating and antitumor compounds in cancer therapy.

Phytosomes: A Promising Nanocarrier for Enhanced Delivery of Herbal Compounds in Cancer Therapy

Cancer is a life-threatening disease that remains a global health problem, with millions of people diagnosed yearly. Despite significant progress in cancer treatment, conventional chemotherapy still faces several limitations, including poor solubility, low bioavailability, lack of selectivity, and severe side effects. Therefore, alternative therapeutic strategies are necessary to improve cancer therapy. This review aimed to provide an updated overview of phytosome complexes and their potential application in cancer therapy, including their formulation techniques, transportation mechanism through phytosome, and recent investigations on their efficacy in treating different types of cancers. In recent years, nanotechnology has emerged as a promising approach to cancer therapy, as it enables the delivery of therapeutic agents to the tumor site with higher selectivity and efficiency. Phytosomes are a nanotechnology-based drug delivery system conjugating plant extracts or phytoconstituents with phospholipids. This conjugation results in the formation of a complex with improved solubility, stability, and bioavailability. Phytosomes have been shown to enhance the pharmacokinetic profile of phytoactive compounds, allowing for better targeting and sustained release. Phytosomes of curcumin, resveratrol, and quercetin have demonstrated anticancer properties in various in vitro and in vivo models. Moreover, phytosomes have been used to deliver chemotherapeutic agents, such as paclitaxel, docetaxel, and camptothecin, with improved efficacy and reduced toxicity. Phytosome complexes offer a promising platform for cancer therapy due to their ability to enhance the bioavailability and efficacy of phytoactive compounds. Incorporating phytosomes in cancer therapy could lead to the development of more effective and less toxic treatments for different types of cancers. Further studies are needed to elucidate the mechanism of action of phytosomes and to optimize their formulation for clinical use.

Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back.

Cancer is a disease of high mortality, and its prevalence has increased steadily in the last few years. However, during the last decade, the development of modern chemotherapy schemes, new radiotherapy techniques, targeted therapies and immunotherapy has brought new hope in the treatment of these diseases. Unfortunately, cancer therapies are also associated with frequent and, sometimes, severe adverse events. Ascorbate (ascorbic acid or vitamin C) is a potent water-soluble antioxidant that is produced in most mammals but is not synthesised endogenously in humans, which lack enzymes for its synthesis. Ascorbate has antioxidant effects that correspond closely to the dose administered. Interestingly, this natural antioxidant induces oxidative stress when given intravenously at a high dose, a paradoxical effect due to its interactions with iron. Importantly, this deleterious property of ascorbate can result in increased cell death. Although, historically, ascorbate has been reported to exhibit anti-tumour properties, this effect has been questioned due to the lack of available mechanistic detail. Recently, new evidence has emerged implicating ferroptosis in several types of oxidative stress-mediated cell death, such as those associated with ischemia–reperfusion. This effect could be positively modulated by the interaction of iron and high ascorbate dosing, particularly in cell systems having a high mitotic index. In addition, it has been reported that ascorbate may behave as an adjuvant of favourable anti-tumour effects in cancer therapies such as radiotherapy, radio-chemotherapy, chemotherapy, immunotherapy, or even in monotherapy, as it facilitates tumour cell death through the generation of reactive oxygen species and ferroptosis. In this review, we provide evidence supporting the view that ascorbate should be revisited to develop novel, safe strategies in the treatment of cancer to achieve their application in human medicine.

Selenium and Platinum Compounds in Cancer Therapy: Potentiality of their Progeny as Future Chemotherapeutics

Abstract:Compounds based on two different elements, selenium and platinum, have been attracting researchers to deploy them in chemotherapy of human cancers. Selenium, as a micronutrient plays many important roles in human biology. Different research groups have been developing both inorganic and organoselenium compounds for potential use for treatment of diseases including cancer. New synthetic designs are emerging to develop selenium compounds either as chemo-preventive or chemotherapeutic agents. Platinum is another important element in cancer therapy. Platinum-based drugs are the first line of treatment for many cancers. Attracted by the fact that chalcogens are excellent ligands for platinum, new ideas are emerging to develop selenium-bound platinum compounds as cancer therapeutics. In this direction, our group has made a beginning to develop stable seleno-platinum compounds to explore their anti-cancer potentials.

Multiresponsive carboxylated graphene oxide-grafted aptamer as a multifunctional nanocarrier for targeted delivery of chemotherapeutics and bioactive compounds in cancer therapy

AbstractTo date, the use of nanocarriers has been developed in various fields, especially in cancer treatment. Graphene oxide (GO) is a novel drug delivery system that eagerly attracts the attention of many researchers due to its unique features. For the first time, a biocompatible AS1411 APT-GO-COOH was synthesized for the co-delivery of chemotherapeutics and herbal drugs. Here, a human gastric adenocarcinoma cell line (AGS) was targeted with aptamer-carboxylated graphene oxide (APT-CGO) containing anticancer drugs (curcumin (CUR) and doxorubicin (DOX)). The current study aimed to assess the anti-cancer effect of combination therapy, as well as target genes and proteins interfering in the development of gastric cancer. After attachment of APT to CGO, the drugs (CUR and DOX) were loaded on the carrier, establishing a co-delivery system. Then, physical characteristics, release profile, cytotoxicity assay, cellular uptake, expression rates of the genes (RB1, CDK2, AKT, and NF-KB) and proteins (RB1, CDK2), and the apoptosis rate were determined. The designed co-delivery system for the drugs (CUR and DOX) and APT showed a thermo- and pH-sensitive drug release behavior that successfully reduced the expression of CDK2, AKT, and NF-KB while it enhanced RB1 expression at the gene and protein levels. Also, APT-CGO-drugs were successfully targeted to the AGS cell line, leading to a highly inhibitory property against this cell line compared to CGO-drugs. It seems that the co-delivery of CUR and DOX along with APT as a targeting agent was more effective than CGO-drugs, suggesting a promising candidate for the treatment of gastric cancer. The results showed that this biofunctionalized nanocarrier could reduce the cytotoxicity of the drugs in normal cells and could increase efficiency.

Cyanobacteria derived compounds: Emerging drugs for cancer management.

The wide diversity of cyanobacterial species and their role in a variety of biological activities have been reported in the previous few years. Cyanobacteria, especially from marine sources, constitutes a major source of biologically active metabolites that have gained great attention especially due to their anticancer potential. Numerous chemically diverse metabolites from various cyanobacterial species have been recognized to inhibit the growth and progression of tumor cells through the induction of apoptosis in many different types of cancers. These metabolites activate the apoptosis in the cancer cells by different molecular mechanisms, however, the dysregulation of the mitochondrial pathway, death receptors signaling pathways, and the activation of several caspases are the crucial mechanisms that got considerable interest. The array of metabolites and the range of mechanisms involved may also help to overcome the resistance acquired by the different tumor types against the ongoing therapeutic agents. Therefore, the primary or secondary metabolites from the cyanobacteria as well as their synthetic derivates could be used to develop novel anticancer drugs alone or in combination with other chemotherapeutic agents. In this study, we have discussed the role of cyanobacterial metabolites in the induction of cytotoxicity and the potential to inhibit the growth of cancer cells through the induction of apoptosis, cell signaling alteration, oxidative damage, and mitochondrial dysfunctions. Moreover, the various metabolites produced by cyanobacteria have been summarized with their anticancer mechanisms. Furthermore, the ongoing trials and future developments for the therapeutic implications of these compounds in cancer therapy have been discussed.

Octyl syringate is preferentially cytotoxic to cancer cells via lysosomal membrane permeabilization and autophagic flux inhibition.

The autophagy-mediated lysosomal pathway plays an important role in conferring stress tolerance to tumor cells during cellular stress such as increased metabolic demands. Thus, targeted disruption of this function and inducing lysosomal cell death have been proved to be a useful cancer therapeutic approach. In this study, we reported that octyl syringate (OS), a novel phenolic derivate, was preferentially cytotoxic to various cancer cells but was significantly less cytotoxic to non-transformed cells. Treatment with OS resulted in non-apoptotic cell death in a caspase-independent manner. Notably, OS not only enhanced accumulation of autophagic substrates, including lapidated LC3 and sequestosome-1, but also inhibited their degradation via an autophagic flux. In addition, OS destabilized the lysosomal function, followed by the intracellular accumulation of the non-digestive autophagic substrates such as bovine serum albumin and stress granules. Furthermore, OS triggered the release of lysosomal enzymes into the cytoplasm that contributed to OS-induced non-apoptotic cell death. Finally, we demonstrated that OS was well tolerated and reduced tumor growth in mouse xenograft models. Taken together, our study identifies OS as a novel anticancer agent that induces lysosomal destabilization and subsequently inhibits autophagic flux and further supports development of OS as a lysosome-targeting compound in cancer therapy. • Octyl syringate, a phenolic derivate, is preferentially cytotoxic to various cancer cells. • Octyl syringate destabilizes the lysosomal function. • Octyl syringate blocks the autophagic flux. • Octyl syringate is a potential candidate compound for cancer therapy.

Abstract 1234: G4 binders as potential immunostimulatory compounds for cancer therapy

Abstract G-quadruplex (G4) is non-canonical nucleic acid structure involved in a plethora of fundamental biological processes. In past decades, it has been studied as a promising pharmaceutical target for anticancer therapy. However, no G4-targeting agent has shown significant clinical effects up to date. Pyridostatin (PDS), a well-known G4 binder, can induce double-stranded DNA breaks and genome instability. We have recently shown that PDS and other G4 binders can trigger micronuclei formation in cancer cells at non-cytotoxic concentrations [1]. As micronuclei can play a crucial role in linking genome instability to innate immunity, we have here wondered whether G4 binders can induce immune gene activation in human MCF-7 breast cancer cells. By using RNA-Seq technology, we show that non-cytotoxic doses of PDS can activate Interferon beta- and IRF3-dependent genes leading to an innate immune gene response in human cancer cells. In addition, immune gene activation follows the induction of micronuclei formation supporting cytoplasmic DNA as a trigger of immune gene activation. Immunofluorescence assays showed that cGAS (a cytoplasmic DNA sensor) can bind to and is activated by micronuclei. In addition, cytostatic PDS concentrations activate STING and IRF3 factors leading to activated immune gene expression. STING inhibition with siRNAs, CRISPR knockout or a chemical inhibitor resulted in a suppression of immune gene expression and Interferon-beta (IFN-B) production in human MCF-7 and murine B16 cell lines, showing that STING is required for PDS-induced immune gene activation in cancer cells. We have then extended the study to a structurally-unrelated G4 binder, PhenDC3, and the results show that PhenDC3 can induce micronuclei formation and IFN-B production in a STING-dependent manner. Then, using TCGA-BRCA dataset, we show that specific gene expression patterns mediated by PDS correlate with immunological hot features of human tumors, such as anti-tumor immune cell infiltration. We could also define a specific PDS gene signature that can predict a better survival of breast cancer patients, suggesting an impact of immunomodulation potential of PDS or other G4 binders in human patients. Thus, our results provide strong evidence that G4 binders can activate innate immune genes in human and murine cancer cells with therapeutic potentials, and that G4 binder-induced micronuclei accumulation can trigger the cGAS-STING signaling pathway. The findings may open to the development of novel immunotherapeutic anticancer strategies based on G4-targeting compounds.