scholarly journals Upgrade of an old drug: Auranofin in innovative cancer therapies to overcome drug resistance and to increase drug effectiveness

2021 ◽  
Author(s):  
Tania Gamberi ◽  
Giovanni Chiappetta ◽  
Tania Fiaschi ◽  
Alessandra Modesti ◽  
Flavia Sorbi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Therapies ◽  
Drug Effectiveness

Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities

2020 ◽  
Vol 20 (14) ◽  
pp. 1114-1131 ◽  
Author(s):  
Kanisha Shah ◽  
Rakesh M. Rawal
Keyword(s):  
Drug Resistance ◽  
Drug Targets ◽  
Complex Disease ◽  
Cancer Therapies ◽  
Altered Expression ◽  
Acquired Drug Resistance ◽  
Challenges And Opportunities ◽  
Chemotherapeutic Treatment ◽  
Epigenetic Modulation ◽  
Targeted Drug Therapies

Cancer is a complex disease that has the ability to develop resistance to traditional therapies. The current chemotherapeutic treatment has become increasingly sophisticated, yet it is not 100% effective against disseminated tumours. Anticancer drugs resistance is an intricate process that ascends from modifications in the drug targets suggesting the need for better targeted therapies in the therapeutic arsenal. Advances in the modern techniques such as DNA microarray, proteomics along with the development of newer targeted drug therapies might provide better strategies to overcome drug resistance. This drug resistance in tumours can be attributed to an individual’s genetic differences, especially in tumoral somatic cells but acquired drug resistance is due to different mechanisms, such as cell death inhibition (apoptosis suppression) altered expression of drug transporters, alteration in drug metabolism epigenetic and drug targets, enhancing DNA repair and gene amplification. This review also focusses on the epigenetic modifications and microRNAs, which induce drug resistance and contributes to the formation of tumour progenitor cells that are not destroyed by conventional cancer therapies. Lastly, this review highlights different means to prevent the formation of drug resistant tumours and provides future directions for better treatment of these resistant tumours.

Targeting cancer-initiating cell drug-resistance: a roadmap to a new-generation of cancer therapies?

2012 ◽  
Vol 17 (9-10) ◽  
pp. 435-442 ◽  
Author(s):  
Angela Alama ◽  
Anna Maria Orengo ◽  
Silvano Ferrini ◽  
Rosaria Gangemi
Keyword(s):  
Drug Resistance ◽  
Cancer Therapies ◽  
New Generation

scholarly journals lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2148 ◽  
Author(s):  
Dominik A. Barth ◽  
Jaroslav Juracek ◽  
Ondrej Slaby ◽  
Martin Pichler ◽  
George A. Calin
Keyword(s):  
Drug Resistance ◽  
Treatment Options ◽  
Cancer Therapies ◽  
Protein Coding ◽  
Genitourinary System ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Novel Therapeutic Strategies ◽  
Regulatory Functions

Available systemic treatment options for cancers of the genitourinary system have experienced great progress in the last decade. However, a large proportion of patients eventually develop resistance to treatment, resulting in disease progression and shorter overall survival. Biomarkers indicating the increasing resistance to cancer therapies are yet to enter clinical routine. Long non-coding RNAs (lncRNA) are non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types of regulatory functions of all known cellular processes. Increasing evidence supports the role of lncRNAs in cancer development and progression. Additionally, their involvement in the development of drug resistance across various cancer entities, including genitourinary malignancies, are starting to be discovered. Consequently, lncRNAs have been suggested as factors in novel therapeutic strategies to overcome drug resistance in cancer. In this review, the existing evidences on lncRNAs and their involvement in mechanisms of drug resistance in cancers of the genitourinary system, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, will be highlighted and discussed to facilitate and encourage further research in this field. We summarize a significant number of lncRNAs with proposed pathways in drug resistance and available reported studies.

scholarly journals Acquired Resistance to Clinical Cancer Therapy: A Twist in Physiological Signaling

2016 ◽  
Vol 96 (3) ◽  
pp. 805-829 ◽  
Author(s):  
Andreas Wicki ◽  
Mario Mandalà ◽  
Daniela Massi ◽  
Daniela Taverna ◽  
Huifang Tang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Immune System ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
Cancer Therapies ◽  
Acquired Drug Resistance ◽  
Physiological Signal

Although modern therapeutic strategies have brought significant progress to cancer care in the last 30 years, drug resistance to targeted monotherapies has emerged as a major challenge. Aberrant regulation of multiple physiological signaling pathways indispensable for developmental and metabolic homeostasis, such as hyperactivation of pro-survival signaling axes, loss of suppressive regulations, and impaired functionalities of the immune system, have been extensively investigated aiming to understand the diversity of molecular mechanisms that underlie cancer development and progression. In this review, we intend to discuss the molecular mechanisms of how conventional physiological signal transduction confers to acquired drug resistance in cancer patients. We will particularly focus on protooncogenic receptor kinase inhibition-elicited tumor cell adaptation through two major core downstream signaling cascades, the PI3K/Akt and MAPK pathways. These pathways are crucial for cell growth and differentiation and are frequently hyperactivated during tumorigenesis. In addition, we also emphasize the emerging roles of the deregulated host immune system that may actively promote cancer progression and attenuate immunosurveillance in cancer therapies. Understanding these mechanisms may help to develop more effective therapeutic strategies that are able to keep the tumor in check and even possibly turn cancer into a chronic disease.

scholarly journals The Role of Cancer Stem Cells in Drug Resistance in Gastroesophageal Junction Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Kate Dinneen ◽  
Anne-Marie Baird ◽  
Ciara Ryan ◽  
Orla Sheils
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Gastroesophageal Junction ◽  
Western World ◽  
Specific Cell ◽  
Cancer Therapies ◽  
Mesenchymal Transition ◽  
Anti Cancer

Gastroesophageal junction adenocarcinomas (GEJA) have dramatically increased in incidence in the western world since the mid-20th century. Their prognosis is poor, and conventional anti-cancer therapies do not significantly improve survival outcomes. These tumours are comprised of a heterogenous population of both cancer stem cells (CSC) and non-CSCs, with the former playing a crucial role in tumorigenesis, metastasis and importantly drug resistance. Due to the ability of CSCs to self-replicate indefinitely, their resistance to anti-cancer therapies poses a significant barrier to effective treatment of GEJA. Ongoing drug development programmes aim to target and eradicate CSCs, however their characterisation and thus identification is difficult. CSC regulation is complex, involving an array of signalling pathways, which are in turn influenced by a number of entities including epithelial mesenchymal transition (EMT), microRNAs (miRNAs), the tumour microenvironment and epigenetic modifications. Identification of CSCs commonly relies on the expression of specific cell surface markers, yet these markers vary between different malignancies and indeed are often co-expressed in non-neoplastic tissues. Development of targeted drug therapies against CSCs thus requires an understanding of disease-specific CSC markers and regulatory mechanisms. This review details the current knowledge regarding CSCs in GEJA, with particular emphasis on their role in drug resistance.

scholarly journals Regulation of signal transduction pathways in colorectal cancer: implications for therapeutic resistance

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12338
Author(s):  
Yeelon Yeoh ◽  
Teck Yew Low ◽  
Nadiah Abu ◽  
Pey Yee Lee
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Abc Transporters ◽  
Advanced Colorectal Cancer ◽  
Drug Efflux ◽  
Cancer Therapies ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Notch Pathways ◽  
Spectrum Of Patients

Resistance to anti-cancer treatments is a critical and widespread health issue that has brought serious impacts on lives, the economy and public policies. Mounting research has suggested that a selected spectrum of patients with advanced colorectal cancer (CRC) tend to respond poorly to both chemotherapeutic and targeted therapeutic regimens. Drug resistance in tumours can occur in an intrinsic or acquired manner, rendering cancer cells insensitive to the treatment of anti-cancer therapies. Multiple factors have been associated with drug resistance. The most well-established factors are the emergence of cancer stem cell-like properties and overexpression of ABC transporters that mediate drug efflux. Besides, there is emerging evidence that signalling pathways that modulate cell survival and drug metabolism play major roles in the maintenance of multidrug resistance in CRC. This article reviews drug resistance in CRC as a result of alterations in the MAPK, PI3K/PKB, Wnt/β-catenin and Notch pathways.

Diverse Targeted Approaches to Battle Multidrug Resistance in Cancer

2019 ◽  
Vol 26 (39) ◽  
pp. 7059-7080 ◽  
Author(s):  
Nagula Shankaraiah ◽  
Shalini Nekkanti ◽  
Ojaswitha Ommi ◽  
Lakshmi Soukya P.S.
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Patient Outcomes ◽  
Associated Factors ◽  
Treatment Strategies ◽  
Cancer Therapies ◽  
Factors Associated ◽  
Treatment Regimens ◽  
Specific Tumor ◽  
Selection Of

: The efficacy of successful cancer therapies is frequently hindered by the development of drug resistance in the tumor. The term ‘drug resistance’ is used to illustrate the decreased effectiveness of a drug in curing a disease or alleviating the symptoms of the patient. This phenomenon helps tumors to survive the damage caused by a specific drug or group of drugs. In this context, studying the mechanisms of drug resistance and applying this information to design customized treatment regimens can improve therapeutic efficacy as well as the curative outcome. Over the years, numerous Multidrug Resistance (MDR) mechanisms have been recognized and tremendous effort has been put into developing agents to address them. The integration of data emerging from the elucidation of molecular and biochemical pathways and specific tumor-associated factors has shown tremendous promise within the oncology community for improving patient outcomes. In this review, we provide an overview of the utility of these molecular and biochemical signaling processes as well as tumor-associated factors associated with MDR, for the rational selection of cancer treatment strategies.

scholarly journals Nanoparticle Formulations of Poly (ADP-ribose) Polymerase Inhibitors for Cancer Therapy

2020 ◽  
Vol 8 ◽  
Author(s):  
Bijay Singh ◽  
Shicheng Yang ◽  
Apurva Krishna ◽  
Srinivas Sridhar
Keyword(s):  
Drug Resistance ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Cancer Therapies ◽  
Current Trends ◽  
Small Molecule Drugs ◽  
Tissue Selectivity ◽  
Reduced Toxicity ◽  
Improved Methods ◽  
Insight Into

A number of poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for clinical use in BRCA mutated and other cancers. However, off-target toxicity of PARP inhibitors and the emergence of drug resistance following prolonged administration of these inhibitors indicate the need for improved methods of drug delivery to the tumors. Nanomedicines based upon nanoparticle formulations of conventional small molecule drugs and inhibitors offer many advantages, such as increased solubility and bioavailability of drugs, reduced toxicity and drug resistance, and improved tissue selectivity and therapeutic efficacy. This review highlights the current trends in formulations of PARP inhibitors developed by nanotechnology approaches and provides an insight into the applications and limitations of these PARP inhibitor nanomedicines for cancer therapies.

Targeting TRIB2 expression with oral antidiabetic drugs to overcome tumour malignancy and drug-resistance

2020 ◽  
Vol 30 (Supplement_2) ◽  
Author(s):  
A Sousa-Coelho
Keyword(s):  
Drug Resistance ◽  
Cell Metabolism ◽  
Data Repository ◽  
Cancer Therapies ◽  
Oral Antidiabetic ◽  
Advanced Search ◽  
Public Data ◽  
Obese Rats ◽  
Public Data Repository ◽  
Marrow Mesenchymal Stem Cells

Abstract Introduction TRIB2 is one of three members of the Tribbles family, which interacts and activates the protein kinase AKT, associated to the suppression of FOXO in melanoma, which mediate insulin action on key functions involved in cell metabolism and growth. TRIB2, recently identified as a druggable protein, has been pointed as a cause of resistance to cancer therapies, and so, modulating its expression might be a suitable strategy to overcome tumour malignancy and drug-resistance. Members from the thiazolidinediones (TZDs) family of oral antidiabetic insulin-sensitizing drugs, available in clinical settings, have been previously reported to be effective in melanoma, however there are still controversial results. Objectives Identifying new therapeutic strategies to overcome therapeutic resistance in TRIB2-positive cancers. Methodology Analyses of TRIB2’s expression levels in different samples in response to TZDs, using GEO profiles available at public data repository with the following advanced search terms: TRIB2 [gene] AND Rosiglitazone OR Pioglitazone OR Troglitazone. Results From a total of 15 independent studies, it was found that TRIB2 was up-regulated in Rosi-treated human dendritic cells, skeletal muscle from obese PCOS women treated with Pioglitazone, and liver from obese rats treated either with Pio or Troglitazone. By contrast, TRIB2 was down-regulated in white adipose tissue (WAT) from obese rats treated either with Pio or Troglitazone, in Rosi-treated mouse stromal vascular cells from inguinal WAT, and in PPARγ–overexpressed marrow mesenchymal stem cells treated with Rosiglitazone. Conclusion Although TRIB2 expression was modulated by the different TZDs in certain samples, depending on the cellular context, it was either up- or down-regulated. While further studies are needed, especially in a malignancy environment, TZDs treatment of TRIB2-positive cancer does not seem to be a valuable therapeutic strategy and might be even counter-productive.

scholarly journals Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signalling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chen Yang ◽  
Chengzhe Tian ◽  
Timothy E. Hoffman ◽  
Nicole K. Jacobsen ◽  
Sabrina L. Spencer
Keyword(s):  
Dna Damage ◽  
Drug Resistance ◽  
Mapk Pathway ◽  
Melanoma Cells ◽  
Cancer Therapies ◽  
Braf Inhibitors ◽  
Anti Cancer ◽  
Genetic Mechanisms ◽  
Pathway Inhibition ◽  
Stress Signalling

AbstractDespite the increasing number of effective anti-cancer therapies, successful treatment is limited by the development of drug resistance. While the contribution of genetic factors to drug resistance is undeniable, little is known about how drug-sensitive cells first evade drug action to proliferate in drug. Here we track the responses of thousands of single melanoma cells to BRAF inhibitors and show that a subset of cells escapes drug via non-genetic mechanisms within the first three days of treatment. Cells that escape drug rely on ATF4 stress signalling to cycle periodically in drug, experience DNA replication defects leading to DNA damage, and yet out-proliferate other cells over extended treatment. Together, our work reveals just how rapidly melanoma cells can adapt to drug treatment, generating a mutagenesis-prone subpopulation that expands over time.

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