Nuclear delivery of dual anti-cancer drugs by molecular self-assembly

2021 ◽  
Vol 9 (1) ◽  
pp. 116-123
Author(s):  
Jindao Wu ◽  
Wenzhou Ding ◽  
Guoyong Han ◽  
Wei You ◽  
Wen Gao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tumor Cells ◽  
Self Assembly ◽  
Nuclear Accumulation ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Good Cell

Nanomedicines generally suffer from poor accumulation in tumor cells, low anti-tumor efficacy, and drug resistance. In order to address these problems, we introduced a novel nanomedicine based on dual anti-cancer drugs, which showed good cell nuclear accumulation properties.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

Biotinylated carboxymethyl chitosan/CaCO3 hybrid nanoparticles for targeted drug delivery to overcome tumor drug resistance

RSC Advances ◽  
2016 ◽  
Vol 6 (73) ◽  
pp. 69083-69093 ◽  
Author(s):  
Jin-Long Wu ◽  
Xiao-Yan He ◽  
Pei-Yuan Jiang ◽  
Meng-Qing Gong ◽  
Ren-Xi Zhuo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Tumor Cells ◽  
Targeted Drug Delivery ◽  
Carboxymethyl Chitosan ◽  
Hybrid Nanoparticles ◽  
Cancer Drug ◽  
Tumor Drug Resistance ◽  
Anti Cancer ◽  
Targeted Drug

A tumor targeted nano-sized self-assembled drug delivery system could efficiently co-deliver an anti-cancer drug and a drug resistance inhibitor to tumor cells and achieve an improved therapeutic efficiency through inhibition of P-gp function.

scholarly journals A Novel Model of Cancer Drug Resistance: Oncosomal Release of Cytotoxic and Antibody-Based Drugs

Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 47 ◽  
Author(s):  
Takanori Eguchi ◽  
Eman Ahmed Taha ◽  
Stuart K. Calderwood ◽  
Kisho Ono
Keyword(s):  
Drug Resistance ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Drug ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Secretory Phenotype ◽  
Novel Model

Extracellular vesicles (EVs), such as exosomes or oncosomes, often carry oncogenic molecules derived from tumor cells. In addition, accumulating evidence indicates that tumor cells can eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing drug resistance phenotype is often coupled with cellular dedifferentiation and transformation in cells undergoing epithelial-mesenchymal transition (EMT), and the adoption of a cancer stem cell phenotype. The release of EVs is also involved in immunosuppression. Herein, we address different aspects by which EVs modulate the tumor microenvironment to become resistant to anticancer and antibody-based drugs, as well as the concept of the resistance-associated secretory phenotype (RASP).

Repurposing Disulfiram as An Anti-Cancer Agent: Updated Review on Literature and Patents

2019 ◽  
Vol 14 (2) ◽  
pp. 113-132 ◽  
Author(s):  
Elmira Ekinci ◽  
Sagar Rohondia ◽  
Raheel Khan ◽  
Qingping P. Dou
Keyword(s):  
Drug Resistance ◽  
Superoxide Dismutase ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Chronic Alcoholism ◽  
New Drugs ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Anti Cancer

Background:Despite years of success of most anti-cancer drugs, one of the major clinical problems is inherent and acquired resistance to these drugs. Overcoming the drug resistance or developing new drugs would offer promising strategies in cancer treatment. Disulfiram, a drug currently used in the treatment of chronic alcoholism, has been found to have anti-cancer activity.Objective:To summarize the anti-cancer effects of Disulfiram through a thorough patent review.Methods:This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy.Results:Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug.Conclusion:For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.

Screening of 129 FDA approved anti-cancer drugs in colorectal cancer cell lines resistant to oxaliplatin or irinotecan (SN38).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Jan Stenvang ◽  
Christine Hjorth Andreassen ◽  
Nils Brünner
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Viability ◽  
Cell Line ◽  
Cell Lines ◽  
Resistant Cell ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Drug Candidates ◽  
Anti Cancer

642 Background: In metastatic colorectal cancer (mCRC) only 3 cytotoxic drugs (oxaliplatin, irinotecan and fluorouracil (5-FU)) are approved and the first and second line response rates are about 50% and 10-15%, respectively. Thus, new treatment options are needed. Novel anti-cancer drug candidates are primarily tested in an environment of drug resistance and the majority of novel drug candidates fail during clinical development. Therefore, “repurposing” of drugs has emerged as a promising strategy to apply established drugs in novel indications. The aim of this project was to screen established anti-cancer drugs to identify candidates for testing in mCRC patients relapsing on standard therapy. Methods: We applied 3 parental (drug sensitive) CRC cell lines (HCT116, HT29 and LoVo) and for each cell line also an oxaliplatin and irinotecan (SN38) resistant cell line. We obtained 129 FDA approved anti-cancer drugs from the Developmental Therapeutics Program (DTP) at the National Cancer Institute (NCI) ( https://dtp.cancer.gov/ ). The parental HT29 cell line and the drug resistant sublines HT29-SN38 and HT29-OXPT were exposed to 3 concentrations of each of the anti-cancer drugs. The effect on cell viability was analyzed by MTT assays. Nine of the drugs were analyzed for effect in the LoVo and HCT116 and the SN38- and oxaliplatin-resistant derived cell lines. Results: None of the drugs caused evident differential response between the resistant and sensitive cells or between the SN38 and oxaliplatin resistant cells. The screening confirmed the resistance as the cells displayed resistance to drugs in the same class as the one they were made resistant to. Of the drugs, 45 decreased cell viability in the HT29 parental and oxaliplatin- or SN-38 resistant cell lines. Nine drugs were tested in all nine CRC cell lines and eight decrease cell viability in the nine cell lines. These included drugs in different classes such as epigenetic drugs, antibiotics, mitotic inhibitors and targeted therapies. Conclusions: This study revealed several possible new “repurposing” drugs for CRC therapy, by showing that 45 FDA-approved anti-cancer drugs decrease cell viability in CRC cell lines with acquired drug resistance.

scholarly journals The role of solvent swelling in the self-assembly of squalene based nanomedicines

Soft Matter ◽  
2015 ◽  
Vol 11 (21) ◽  
pp. 4173-4179 ◽  
Author(s):  
Debasish Saha ◽  
Fabienne Testard ◽  
Isabelle Grillo ◽  
Fatima Zouhiri ◽  
Didier Desmaele ◽  
...  
Keyword(s):  
Self Assembly ◽  
The Self ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Role Of Solvent ◽  
Solvent Swelling

Squalene based nanoparticles obtained via nanoprecipitation are promising candidates as efficient anti-cancer drugs.

Clinical relevance of the molecular mechanisms of resistance to anti-cancer drugs

1999 ◽  
Vol 1 (15) ◽  
pp. 1-21 ◽  
Author(s):  
Robert Brown ◽  
Matthew Links
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Positive Response ◽  
Cancer Drug ◽  
Clinical Relapse ◽  
Cancer Drugs ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Or Genes ◽  
Clinical Drug

Resistance to anti-cancer drugs (drug resistance) can be defined in the laboratory by the amount of anti-cancer drug that is required to produce a given level of cell death (drug response). Clinical drug resistance can be defined either as a lack of reduction of the size of a tumour following chemotherapy or as the occurrence of clinical relapse after an initial ‘positive’ response to anti-tumour treatment. Many studies of tumour samples do not directly measure drug resistance in the laboratory (because it is difficult to perform functional assays on tumour tissue); instead, key proteins or genes that are involved in particular mechanisms of drug resistance have been proposed as ‘markers’ of drug resistance. In this review, we have focused on the problems that can arise when attempts are made to relate the relevance of laboratory-identified molecular mechanisms of drug resistance to anti-cancer drug resistance that occurs in patients.

scholarly journals Potential role of transforming growth factor beta1 in drug resistance of tumor cells.

2003 ◽  
Vol 50 (2) ◽  
pp. 497-508 ◽  
Author(s):  
Rostyslav Stoika ◽  
Mariya Yakymovych ◽  
Serhiy Souchelnytskyi ◽  
Ihor Yakymovych
Keyword(s):  
Signal Transduction ◽  
Drug Resistance ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Signal Transduction Pathway ◽  
Target Cells ◽  
Type I ◽  
Transduction Pathway ◽  
L1210 Cells ◽  
Anti Cancer

Acquired drug resistance of tumor cells is frequently observed in cancer patients undergoing chemotherapy. We studied murine leukemia L1210 cells sensitive and resistant to the cytotoxic action of cisplatin and showed that cisplatin-resistant leukemia cells were also refractory to TGF beta1-dependent growth inhibition and apoptosis. Addressing the question about the mechanisms responsible for the cross-resistance to cisplatin and TGF beta1, we found that cisplatin- and TGF beta1-resistant L1210 cells possessed a decreased expression of type I TGF beta1 receptor, while the expression of type II TGF beta1 receptor was not affected. Western blot analysis of Smad proteins 2, 3, 4, 6, and 7, which participate in signal transduction pathway down-stream of the TGF beta1 receptors, revealed an increased expression of Smad 6, inhibiting TGF beta1 action, only in cisplatin- and TGF beta1-resistant L1210 cells. TGF beta1 and especially the cytotoxic mistletoe agglutinin increased Smad 6 expression in TGF beta1-sensitive but not in TGF beta1-resistant L1210 cells. TGF beta1-resistant L1210 cells also differed from TGF beta1-sensitive cells by the lack of expression of the pro-apoptotic p53 protein and higher level of expression of the anti-apoptotic Bcl-2 protein. Thus, the described co-expression of tumor cell refractoriness to an anti-cancer drug and to the inhibitory cytokine TGF beta1 is accompanied by multiple changes in the TGF beta1 signal transduction pathway and in other regulatory systems of the target cells. Besides, we found that various anti-tumor drugs and cytotoxic plant lectins increased the level of TGF beta1 expression in both TGFbeta1-sensitive and -resistant L1210 cells. A hypothesis is proposed that TGFbeta1 can at least partly mediate the effect of cell-stressing agents and, thus, the development of TGF beta1 resistance may be responsible for the appearance of tumor cell refractoriness to the action of some anti-cancer drugs.

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