Action In Cancer Therapy Research Articles

Development of pH-Sensitive Magnetoliposomes Containing Shape Anisotropic Nanoparticles for Potential Application in Combined Cancer Therapy.

Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.

Nanovaccines for Cancer Prevention and Immunotherapy: An Update Review.

Simple SummaryCancer vaccines are a promising immunotherapy-based agents used in cancer therapy. However, monotherapy with these vaccines does not have the sufficient effectiveness in clinical settings. To overcome this challenge, researchers designed nanosystems that increase cancer vaccine efficacy and effectiveness by improving the vaccine's half-life and durability, inducing TME reprogram-ming, and enhancing the anti-tumor immunity with minimum toxicity. This review summarized the structure and different types of cancer nanovaccines and their mechanisms of action in cancer therapy. Moreover, the advantages and drawbacks of these vaccines are discussed.Cancer immunotherapy has received more and more attention from cancer researchers over the past few decades. Various methods such as cell therapy, immune checkpoint blockers, and cancer vaccines alone or in combination therapies have achieved relatively satisfactory results in cancer therapy. Among these immunotherapy-based methods, cancer vaccines alone have not yet had the necessary efficacy in the clinic. Therefore, nanomaterials have increased the efficacy and ef-fectiveness of cancer vaccines by increasing their half-life and durability, promoting tumor mi-croenvironment (TME) reprogramming, and enhancing their anti-tumor immunity with minimal toxicity. In this review, according to the latest studies, the structure and different types of nanovaccines, the mechanisms of these vaccines in cancer treatment, as well as the advantages and disadvantages of these nanovaccines are discussed.

Nanocluster-Based Drug Delivery and Theranostic Systems: Towards Cancer Therapy.

Over the last decades, the global life expectancy of the population has increased, and so, consequently, has the risk of cancer development. Despite the improvement in cancer therapies (e.g., drug delivery systems (DDS) and theranostics), in many cases recurrence continues to be a challenging issue. In this matter, the development of nanotechnology has led to an array of possibilities for cancer treatment. One of the most promising therapies focuses on the assembly of hierarchical structures in the form of nanoclusters, as this approach involves preparing individual building blocks while avoiding handling toxic chemicals in the presence of biomolecules. This review aims at presenting an overview of the major advances made in developing nanoclusters based on polymeric nanoparticles (PNPs) and/or inorganic NPs. The preparation methods and the features of the NPs used in the construction of the nanoclusters were described. Afterwards, the design, fabrication and properties of the two main classes of nanoclusters, namely noble-metal nanoclusters and hybrid (i.e., hetero) nanoclusters and their mode of action in cancer therapy, were summarized.

Abstract 18: Cancer Control Assessments in Low- and Middle-Income Countries during COVID-19: The IAEA-IARC-WHO imPACT Review Hybrid Modality

Abstract Purpose: Under the auspices of the WHO-IAEA Joint Programme on Cancer Control, the International Atomic Energy Agency's (IAEA) Programme of Action for Cancer Therapy (PACT) supports Member States through assessments of national cancer control capacities and needs (imPACT Reviews) related to the cancer continuum. imPACT Reviews are conducted jointly with the World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and other partners as appropriate. To ensure continuity of imPACT Reviews to Member States during the COVID-19 pandemic, in particular to low- and middle- income countries, a hybrid modality with a virtual component has been adopted. Methods: With the hybrid modality, imPACT Reviews are conducted partially virtually through online meetings with stakeholders/international experts (using photos, videos and live walk-throughs of health facilities), and through in-country visits when travel restrictions are lifted to validate findings and engage with national authorities. Results: The case studies of Senegal and Mali initiated in mid-2020 demonstrate the effectiveness of the hybrid modality. Review findings and recommendations have been consolidated into preliminary reports submitted to the respective Ministries of Health in December 2020 and considering the impact of COVID-19 on cancer-related health services. The Reviews featured a cervical and paediatric cancer focus in line with WHO global initiatives and national priorities. Immediate next steps for the countries are the development of costed national cancer control plans and support in mobilizing resources. Conclusion: The coordinated efforts of IAEA, IARC and WHO ensured continuity of evidence-based cancer control assessments and the virtual component may be considered for future imPACT Reviews. Benefits include involving a higher number of institutions and experts, minimizing disruption to their work, visiting more health facilities, and ensuring sustained dialogue over a longer period of time. This contributes to a stronger collaborative network while enhancing government engagement and national ownership. Citation Format: Marianna Nobile, Kendall Siewert, Maria Tena Perpina, Yuliya Lyamzina. Cancer Control Assessments in Low- and Middle-Income Countries during COVID-19: The IAEA-IARC-WHO imPACT Review Hybrid Modality [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 18.

Development of Store-Operated Calcium Entry-Targeted Compounds in Cancer.

Store-operated Ca2+ entry (SOCE) is the major pathway of Ca2+ entry in mammalian cells, and regulates a variety of cellular functions including proliferation, motility, apoptosis, and death. Accumulating evidence has indicated that augmented SOCE is related to the generation and development of cancer, including tumor formation, proliferation, angiogenesis, metastasis, and antitumor immunity. Therefore, the development of compounds targeting SOCE has been proposed as a potential and effective strategy for use in cancer therapy. In this review, we summarize the current research on SOCE inhibitors and blockers, discuss their effects and possible mechanisms of action in cancer therapy, and induce a new perspective on the treatment of cancer.

Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin in Cancer Therapy.

Cisplatin and other platinum-based chemotherapeutic drugs have been used extensively for the treatment of human cancers such as bladder, blood, breast, cervical, esophageal, head and neck, lung, ovarian, testicular cancers, and sarcoma. Cisplatin is commonly administered intravenously as a first-line chemotherapy for patients suffering from various malignancies. Upon absorption into the cancer cell, cisplatin interacts with cellular macromolecules and exerts its cytotoxic effects through a series of biochemical mechanisms by binding to Deoxyribonucleic acid (DNA) and forming intra-strand DNA adducts leading to the inhibition of DNA synthesis and cell growth. Its primary molecular mechanism of action has been associated with the induction of both intrinsic and extrinsic pathways of apoptosis resulting from the production of reactive oxygen species through lipid peroxidation, activation of various signal transduction pathways, induction of p53 signaling and cell cycle arrest, upregulation of pro-apoptotic genes/proteins, and down-regulation of proto-oncogenes and anti-apoptotic genes/proteins. Despite great clinical outcomes, many studies have reported substantial side effects associated with cisplatin monotherapy, while others have shown substantial drug resistance in some cancer patients. Hence, new formulations and several combinational therapies with other drugs have been tested for the purpose of improving the clinical utility of cisplatin. Therefore, this review provides a comprehensive understanding of its molecular mechanisms of action in cancer therapy and discusses the therapeutic approaches to overcome cisplatin resistance and side effects.

Plant Mediated Silver Nanoparticles and Mode of Action in Cancer Therapy: A Review.

Cancer is a widespread fatal disease associated with the abnormal growth of cells in the body. This article represents applications of biologically synthesized silver nanoparticles and their mode of action in cancer therapy. Nanomedicines have been proved to be an effective therapy in the treatment of the disease because of a wide range of applications. Due to the small shape and size, these nanoparticles are emerging to be of novel importance. They are abundantly found in various resources with easy extraction. Biologically synthesized silver nanoparticles are safe for humans as well as for the environment. They may replace the harmful therapies like chemotherapy, etc. used in cancer treatment due to the severe side effects associated with it. Sometimes patient may die because of the side effects. These green nanoparticles have great potential to treat and diagnose different cancers. This article laid a research opportunity for the diagnosis and treatment of cancer.

Identifying cancer-related molecular targets of Nandina domestica Thunb. by network pharmacology-based analysis in combination with chemical profiling and molecular docking studies.

The fruits of Nandina domestica Thunb. have served as folk medicines in Chinese and Japanese tradition for treatment of several tumors including pharynx tumor and tooth abscess for many years, yet its exact mechanism of action is not yet known. The study targets the identification of the main constituents of the fruits extracts and investigation of their mode of action in cancer therapy via pharmacology-based analysis and molecular docking. The different extracts of N. domestica Thunb. were analyzed via UPLC-MS/MS for identification of their active constituents. STITCH, DAVID, KEGG and STRING database were utilized for construction of compound-target and compound-target-pathway networks using Cytoscape 3.2.1. Molecular docking analysis of the top hit compounds was performed against the identified top hit molecular targets in the constructed networks. In vitro-testing of Nandina domestica Thunb. against colorectal cancer cell lines was carried out and correlated to the chemical profile of the extract to identify important biomarkers. The ADME properties of the active compounds were also evaluated. 22 compounds were identified by UPLC-MS/MS analysis and were forwarded to network pharmacology-based analysis. Results showed the enrichment of 5 compounds and 4 molecular targets in the network namely; AKT1, CASP3, MAPK1 and TP53. The pathway analysis of the identified targets revealed that 15 cancer-related pathways were enriched including colorectal cancer, endometrial cancer and small-cell lung cancer. In-vitro testing of the extracts against colo-rectal cancer cell lines revealed the fractions enriched in the identified hit compounds were indeed the most active as revealed from the HCA-heat-map. ADME results showed that all compounds were drug-like candidates showing acceptable values according to Lipinski's rule. Network pharmacology analysis revealed that the compounds isoquercitrin, quercitrin, berberine, chlorogenic acid and caffeic acid showed strong synergistic interactions with the cancer-related targets and pathways. It could be concluded that N. domestica Thunb. constituents affect both apoptosis and Akt-signaling pathways during the stages of early and intermediate adenoma through interaction with the targets CASP3 and MAPK1 (ErC2) while during the stages of late adenoma and carcinoma, the compounds acts through the p53 and ErbB signaling pathways.

The effect of linkers on the self-assembling and anti-tumor efficacy of disulfide-linked doxorubicin drug-drug conjugate nanoparticles

Drug-drug conjugate nanoparticles (DDC NPs) is a potential method for overcoming poor solubility and nonspecific action in cancer therapy, which is based on its high drug loading efficiency and passive tumor-target properties. Our laboratory has prepared DOX-SS-DOX NPs based on disulfide-linked doxorubicin (DOX) drug-drug conjugate, which showed well physical stability and similar anti-tumor efficacy as liposomes. However, how structures of DDCs influence the self-assembling and anti-tumor efficacy is still seldom clarified and needs further investigation. Here, we discussed the role of linker types, length and linkage site in the NPs self-assembling and anti-tumor efficacy. A series of DOX prodrugs were prepared and all the prodrugs could self-assemble into NPs except DOX-SS-DOX (2), indicating the linker length played an important role during self-assembling process. The linkage sites and types of linker exhibited great influence on in vitro cytotoxicity and in vivo anti-tumor efficacy, particularly, modification on C-14 hydroxyl was more efficient for DOX release than on amino group. Besides, disulfide-bond was not cleaved and DOX-SH release did not occur in the metabolism process. The function of disulfide-bond was to enhance the release of DOX in the hydrolysis process. These findings is meaningful for effective prodrug NPs design for therapeutics.

Effect of silibinin-loaded nano-niosomal coated with trimethyl chitosan on miRNAs expression in 2D and 3D models of T47D breast cancer cell line

Silibinin is a natural flavonoid with a strong antioxidant property and weak cytotoxic activity. It has demonstrated anti-tumoural activity against many types of malignancies; however, due to its hydrophobic structure, it has poor water solubility, bioavailability and permeability across intestinal epithelial cells. To improve the effect of silibinin, we have vehiculated silibinin by a highly stable niosomal nanostructure based on a Span 60/cholesterol (CH)/N-trimethyl chitosan (TMC) system in order to study its potential application for the delivery of silibinin in T47D cultured under three-dimensional (3D) and two-dimensional (2D) conditions. To study the effect of nanodrug on miRNAs expression, we evaluated quantitative expression of miRNA-21 and miRNA-15a as well as miR-141 and miR-200c which act as oncogene and tumour suppressors by real-time PCR. Results demonstrated that the mechanism of nanodrug action as well as the response of tumour cells differed in 3D culture as compared to 2D. Delivery of silibinin-loaded niosomes coated with TMC was found to be more effective in inhibiting the growth of tumour cells and inducing apoptosis than free silibinin administration. In silibinin‐treated cells, death occurred in a dose- and time- dependent manner by induction of apoptosis and alteration of the cell cycle. Real-time PCR analysis revealed a decrease in miR-21, miR-15a and miR-141while increase in miR-200c expression levels was observed in silibinin-treated cells relative to the levels in the untreated cells. The results show that nanodrug delivery was more effective than free silibinin administration in changing the level of miRNAs expression in cancer cells. Therefore, niosomal nanostructure with TMC could be a suitable vehicle for hydrophobic compounds, such as silibinin, by improving their action in cancer therapy.

Building the Global Cancer Workforce: Assessing the Cancer Research and Control Progress of Low- and Middle-Income Country Participants in the National Cancer Institute Summer Curriculum in Cancer Prevention

Abstract 48 Background: The National Cancer Institute (NCI) Summer Curriculum in Cancer Prevention, hosted by NCI’s Cancer Prevention Fellowship Program, has provided interdisciplinary training to physicians, scientists, nurses, and other cancer health care professionals in the principles and practice of cancer prevention, control, and molecular biology and genetics. Since 1998, the summer curriculum has enrolled an increasing number of international participants, with many nominees from All-Ireland NCI Cancer Consortium and the International Atomic Energy Agency’s Programme of Action for Cancer Therapy. NCI’s Center for Global Health selects meritorious international participants, specifically from low- and middle-income countries (LMICs), and has offered limited travel and subsistence scholarships. In spring 2016, the Center for Global Health conducted an evaluation of LMIC participants from 1999 to 2015 to assess the impact of the summer curriculum on participants’ engagement and activities in cancer research and control, including peer-reviewed publications, grants received, scientific presentations, cancer control planning, and advocacy. Methods: We surveyed participants about these topics by using an electronic survey system (Questionnaire Design Studio, v3.0) and analyzed responses in SPSS (SPSS, Chicago, IL) and Excel (Microsoft, Redmond, WA). Results: Of 427 LMIC participants from 1999 to 2015, 357 were surveyed via e-mail invitations to an online survey link, of which 156 responded (44%) during a 4-week study period with follow-up. Overall, 97% report using the knowledge and skills acquired frequently or sometimes, and 80% reported training at least one other person in course content. Nearly 50% reported publishing and 27% reported receiving research funding, of which 84% had not received a grant before participation. Conclusion: Participation of international attendees at the NCI Summer Curriculum builds a global cancer community, utilizing the expertise of Cancer Prevention Fellowship Program in training the cancer health care workforce. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from either author.

Reverse micelles-in-microspheres with sustained release of water-soluble combretastatin A4 phosphate for S180 tumor treatment.

Combretastatin A4 phosphate (CA4P), the water-soluble phosphate pro-drug of combretastatin A4 (CA4), acts as a novel vascular disrupting agent (VDA). It strongly inhibits tubulin polymerization and selectively exerts action against tumor blood vessels. However, its quite short half-life (∼30 min) results in a short action time and consequently limits its application. Therefore, it is beneficial to develop a sustained-release preparation of CA4P for relatively long action duration. On the other hand, conventional PLGA microspheres display poor encapsulation capability for water-soluble small molecules due to rapid diffusion outside. Hence, we developed CA4P-loaded microspheres (CA4P-MS) composed of methoxy poly(ethylene glycol)-b-polylactide (PELA) reverse micelles and PLGA with a nano-in-micro sea-island structure. The CA4P encapsulation efficiency of CA4P-MS reached 92.88%. More interestingly, sustained drug release was achieved, which contributed to the prolonged inhibition effect on S180 tumor during a 30-day period with one-time subcutaneous administration. In conclusion, our study established a biodegradable polymer based platform to construct microspheres for water-soluble small molecular compounds with sustained release and a long-lasting action.

Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line.

Introduction : Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results : Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG-Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

DNA Origami Delivery System for Cancer Therapy with Tunable Release Properties

In the assembly of DNA nanostructures, the specificity of Watson-Crick base pairing is used to control matter at the nanoscale. Using this technology for drug delivery is a promising route toward the magic bullet concept, as it would allow the realization of complex assemblies that co-localize drugs, targeting ligands and other functionalities in one nanostructure. Anthracyclines' mechanism of action in cancer therapy is to intercalate DNA, and since DNA nanotechnology allows for such a high degree of customization, we hypothesized that this would allow us to tune the DNA nanostructures for optimal delivery of the anthracycline doxorubicin (Dox) to human breast cancer cells. We have tested two DNA origami nanostructures on three different breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7). The different nanostructures were designed to exhibit varying degrees of global twist, leading to different amounts of relaxation in the DNA double-helix structure. By tuning the nanostructure design we are able to (i) tune the encapsulation efficiency and the release rate of the drug and (ii) increase the cytotoxicity and lower the intracellular elimination rate when compared to free Dox. Enhanced apoptosis induced by the delivery system in breast cancer cells was investigated using flow cytometry. The findings indicate that DNA origami nanostructures represent an efficient delivery system for Dox, resulting in high degrees of internalization and increased induction of programmed cell death in breast cancer cells. In addition, by designing the structures to exhibit different degrees of twist, we are able to rationally control and tailor the drug release kinetics.

Orally Administered Particulate β-Glucan Modulates Tumor-Capturing Dendritic Cells and Improves Antitumor T-Cell Responses in Cancer

The beneficial properties of β-glucans have been recognized for centuries. Their proposed mechanisms of action in cancer therapy occur via stimulation of macrophages and priming of innate neutrophil complement receptor 3 for eliciting complement receptor 3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. The current study is to investigate whether β-glucan therapy has any effect on antitumor adaptive T-cell responses. We first examined the trafficking of orally administered particulate yeast-derived β-glucan and its interaction with dendritic cells (DC) that captured tumor materials. Antigen-specific T cells were adoptively transferred into recipient mice to determine whether oral β-glucan therapy induces augmented T-cell responses. Lewis lung carcinoma and RAM-S lymphoma models were used to test oral β-glucan therapeutic effect. Further mechanistic studies including tumor-infiltrating T cells and cytokine profiles within the tumor milieu were determined. Orally administered particulate β-glucan trafficked into spleen and lymph nodes and activated DCs that captured dying tumor cells in vivo, leading to the expansion and activation of antigen-specific CD4 and CD8 T cells. In addition, IFN-γ production of tumor-infiltrating T cells and CTL responses were significantly enhanced on β-glucan treatment, which ultimately resulted in significantly reduced tumor burden. Moreover, β-glucan-treated tumors had significantly more DC infiltration with the activated phenotype and significant levels of Th1-biased cytokines within the tumor microenvironment. These data highlight the ability of yeast-derived β-glucan to bridge innate and adaptive antitumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy.

TARGETING OF TUMOR CELLS BY LIPOSOMES – ENCAPSULATED MISONIDAZOL

The effect of liposomal drug encapsulation on the distribution pattern of the encapsulated drug, in tumor and normal tissues of tumor-bearing mouse, was studied. The radioactivity content in some selected organs and serum, after administration of 14C- Labelled misonidazole, was followed at different time intervals. Depending on liposomal the drug formulation type, the uptake of the drug into normal tissue and serum was found to be variable and could be arranged in the following descending order drug fee form > Small unilamellar liposomally encapsulated drug > multilamellar liposomally encapsulated drug On the contrary, the uptake of the drug into tumor tissues was greatest for multilamellar liposomal form, less for small unilamellar liposomes and least for drug fee form. Also, the half-time (t1/2) for drug clearance was longest for multilamellar liposome, less for small unilamellar liposome and least for drug free form .However, for both liposomal types, the half-time for drug clearance was longest for positively charged liposomes and least for negatively charged type. It could be concluded that multilamellar liposomes with positive surface charge represented an optimal or most suitable formnulation for modulating drug action in cancer therapy and targeting the drug to the selected site of action.

Polymerase chain reaction analysis of cisplatin-induced mitochondrial DNA damage in human ovarian carcinoma cells.

The purpose of this study was to determine whether the observed synergistic interaction between cisplatin and valinomycin (VM) in human ovarian carcinoma is the result of mitochondrial DNA (mtDNA) damage. A polymerase chain reaction (PCR)-based method was used to quantitate the lesion frequencies produced by cisplatin, VM and/or drug combination in a 1.1 kbp segment of mtDNA and a 0.536 kbp segment of the nuclear-located beta-globin gene in human ovarian CaOV-3 carcinoma cells. Our data indicates that the nuclear DNA (nDNA) received more cisplatin-induced damage at doses of 25 microM or less than did mtDNA. At higher cisplatin doses (50 microM or more), however, the damage was relatively equal in both segments. VM alone produced little or no damage on mtDNA, yet a significant amount of damage was detected within nDNA. However, when 1 microM VM was used in combination with low doses of cisplatin (0-40 microM), extensive mtDNA damage was detected as compared with the absence of detectable damage on nDNA. In mtDNA, the lesion frequency was 5.45 lesions/10 kb/10 microM cisplatin in the presence of 1 microM VM, whereas no detectable lesions were induced by cisplatin alone. This drug combination produced no detectable damage on DNA, indicating that cisplatin-induced mtDNA damage could be the basis for the observed synergistic interaction with VM. These results also correlate well with our recent in vivo study with the nude mice model of human ovarian cancer treated with a cisplatin/liposomal VM drug combination. Furthermore, this report shows evidence for the role of mitochondria and mtDNA as alternative targets for drug action in cancer therapy.