scholarly journals Mechanisms of drug resistance in ovarian cancer

2021 ◽  
Vol 11 (9) ◽  
pp. 362-367
Author(s):  
Klaudia Żak ◽  
Michał Piwoński ◽  
Paweł Stanicki ◽  
Karolina Kalicka ◽  
Justyna Nowaczek
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Relevant Literature ◽  
Resistance Mechanisms ◽  
Screening Tools ◽  
Advanced Stage ◽  
Gynecological Cancers ◽  
Common Cancer ◽  
Specific Symptoms

Ovarian cancer is the fifth most common cancer affecting women and the most lethal cancer among the gynecological cancers. Because of the lack of specific symptoms and no special screening tools, it is recognised in an advanced stage. In addition, drug resistance in ovarian cancer is so frequent, that genes and cross-talks between some important pathways are still analysed. In this review, the major and recently identified molecular mechanisms of drug resistance, including platinum, taxane, bevacizumab and PARPi resistance mechanisms in ovarian cancer from relevant literature have been investigated.

scholarly journals Mechanisms and Advances in Anti-Ovarian Cancer with Natural Plants Component

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5949
Author(s):  
Jingyuan Wu ◽  
Tuoyu Zhou ◽  
Yinxue Wang ◽  
Yanbiao Jiang ◽  
Yiqing Wang
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Therapeutic Effects ◽  
Dna Lesion ◽  
Female Reproductive Health ◽  
Wide Availability

Ovarian cancer ranks seventh in the most common malignant tumors among female disease, which seriously threatens female reproductive health. It is characterized by hidden pathogenesis, missed diagnosis, high reoccurrence rate, and poor prognosis. In clinic, the first-line treatment prioritized debulking surgery with paclitaxel-based chemotherapy. The harsh truth is that female patients are prone to relapse due to the dissemination of tumor cells and drug resistance. In these circumstances, the development of new therapy strategies combined with traditional approaches is conductive to improving the quality of treatment. Among numerous drug resources, botanical compounds have unique advantages due to their potentials in multitarget functions, long application history, and wide availability. Previous studies have revealed the therapeutic effects of bioactive plant components in ovarian cancer. These natural ingredients act as part of the initial treatment or an auxiliary option for maintenance therapy, further reducing the tumor and metastatic burden. In this review, we summarized the functions and mechanisms of natural botanical components applied in human ovarian cancer. We focused on the molecular mechanisms of cell apoptosis, autophagy, RNA and DNA lesion, ROS damage, and the multiple-drug resistance. We aim to provide a theoretical reference for in-depth drug research so as to manage ovarian cancer better in clinic.

Tuberculosis: An Update on Pathophysiology, Molecular Mechanisms of Drug Resistance, Newer Anti-TB Drugs, Treatment Regimens and Host-Di-rected Therapies

2020 ◽  
Vol 21 ◽  
Author(s):  
Pobitra Borah ◽  
Pran Kishore Deb ◽  
Katharigatta N. Venugopala ◽  
Nizar A. Al-Shar’i ◽  
Vinayak Singh ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Cellular Functions ◽  
Pathogenic Potential ◽  
Treatment Regimens ◽  
Latent Tb ◽  
Clinical Advances ◽  
Anti Hiv ◽  
Molecular Interventions

Abstract: The human tuberculosis (TB) is primarily caused by Mycobacterium tuberculosis (Mtb) that inhabits inside and amidst immune cells of the host with adapted physiology to regulate interdependent cellular functions with intact pathogenic potential. The complexity of this disease is attributed to various factors such as the reactivation of latent TB form after prolonged persistence, disease progression specifically in immunocompromised patients, advent of multi- and extensively-drug resistant (MDR and XDR) Mtb strains, adverse effects of tailor-made regimens, and drug-drug interactions among anti-TB drugs and anti-HIV therapies. Thus there is a compelling demand for newer anti-TB drugs or regimens to overcome these obstacles. Considerable multifaceted transformations in the current TB methodologies and molecular interventions underpinning host-pathogen interactions and drug resistance mechanisms may assist to overcome the emerging drug re-sistance. Evidently, recent scientific and clinical advances have revolutionised the diagnosis, prevention and treatment of all forms of the disease. This review sheds light on the current understanding of the pathogenesis of TB disease, molecular mechanisms of drug-resistance, progress on the development of novel or repurposed anti-TB drugs and regimens, host-directed therapies, with particular emphasis on underlying knowledge gaps and prospective for futuristic TB control pro-grams.

An Overview of Ovarian Cancer: Molecular Processes Involved and Devel-opment of Target-based Chemotherapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Basheerulla Shaik ◽  
Tabassum Zafar ◽  
Krishnan Balasubramanian ◽  
Satya P. Gupta
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Western World ◽  
Advanced Stage ◽  
Molecular Processes ◽  
Common Cause ◽  
The Past ◽  
Theoretical Approaches ◽  
Statistical Studies ◽  
Made In

: Ovarian cancer is one of the leading gynecologic diseases with a high mortality rate worldwide. Current statistical studies on cancer reveals that over the past two decades the fifth most common cause of death related to cancer in females of the western world is this ovarian cancer. In spite of significant strides made in genomics, proteomics and radiomics, there has been little progress in transitioning these research advances into effective clinical administration of ovarian cancer. Consequently, researchers have diverted their attention to find various molecular processes involved in the development of this cancer and how these processes can be exploited to develop potential chemotherapeutics to treat this cancer. The present review gives an overview of these studies which may update the researchers where we stand and where to go further. Un-fortunate situation with ovarian cancer that still exists is that most patients with it do not show any symptoms until the disease has moved to an advanced stage. Undoubtedly, several targets-based drugs have been developed to treat it, but drug-resistance and the recurrence of this disease is still a problem. For the development of potential chemotherapeutics for ovarian cancer, however, some theoretical approaches have also been applied. A description of such methods and their success in this direction is also covered in this review.

scholarly journals Quantitative proteomics analysis of Mycoplasma pneumoniae identifies potential macrolide resistance determinants

2020 ◽  
Author(s):  
shaoli li ◽  
guanhua xue ◽  
hanqing zhao ◽  
yanling feng ◽  
chao yan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycoplasma Pneumoniae ◽  
Quantitative Proteomics ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Community Acquired Pneumonia ◽  
Proteomics Analysis ◽  
Tandem Mass Tag ◽  
Peptide Biosynthesis ◽  
Resistant Strains

Abstract Mycoplasma pneumoniae is one of the leading causes of community-acquired pneumonia in children and adolescents. Because of the wide application of macrolides in clinical treatment, macrolide-resistant M. pneumoniae strains have become increasingly common worldwide. However, the molecular mechanisms underlying drug resistance in M. pneumoniae are poorly understood. In the present work, we analyzed the whole proteomes of macrolide-sensitive and macrolide-resistant strains of M. pneumoniae using a tandem mass tag-labeling quantitative proteomic technique, Data are available via ProteomeXchange with identifier PXD022220. In total, 165 differentially expressed proteins were identified, of which 80 were upregulated and 85 were downregulated in the drug-resistant strain compared with the sensitive strain. Functional analysis revealed that these proteins were predominantly involved in protein and peptide biosynthesis processes, the ribosome, and transmembrane transporter activity, which implicates them in the mechanism(s) of resistance of M. pneumoniae to macrolides. Our results provide new insights into drug resistance in M. pneumoniae and identify potential targets for further studies on resistance mechanisms in this bacterium.

scholarly journals Quantitative proteomics analysis of Mycoplasma pneumoniae identifies potential macrolide resistance determinants

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaoli Li ◽  
Guanhua Xue ◽  
Hanqing Zhao ◽  
Yanling Feng ◽  
Chao Yan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycoplasma Pneumoniae ◽  
Quantitative Proteomics ◽  
Molecular Mechanisms ◽  
Resistance Mechanisms ◽  
Community Acquired Pneumonia ◽  
Proteomics Analysis ◽  
Tandem Mass Tag ◽  
Peptide Biosynthesis ◽  
Resistant Strains

AbstractMycoplasma pneumoniae is one of the leading causes of community-acquired pneumonia in children and adolescents. Because of the wide application of macrolides in clinical treatment, macrolide-resistant M. pneumoniae strains have become increasingly common worldwide. However, the molecular mechanisms underlying drug resistance in M. pneumoniae are poorly understood. In the present work, we analyzed the whole proteomes of macrolide-sensitive and macrolide-resistant strains of M. pneumoniae using a tandem mass tag-labeling quantitative proteomic technique, Data are available via ProteomeXchange with identifier PXD022220. In total, 165 differentially expressed proteins were identified, of which 80 were upregulated and 85 were downregulated in the drug-resistant strain compared with the sensitive strain. Functional analysis revealed that these proteins were predominantly involved in protein and peptide biosynthesis processes, the ribosome, and transmembrane transporter activity, which implicates them in the mechanism(s) of resistance of M. pneumoniae to macrolides. Our results provide new insights into drug resistance in M. pneumoniae and identify potential targets for further studies on resistance mechanisms in this bacterium.

scholarly journals An Overview of Candidate Therapeutic Target Genes in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1470
Author(s):  
Elena Alexandrova ◽  
Giovanni Pecoraro ◽  
Assunta Sellitto ◽  
Viola Melone ◽  
Carlo Ferravante ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Frequency ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Molecular Signature ◽  
Loss Of Function ◽  
Current Therapies ◽  
Tumor Growth And Metastasis ◽  
Specific Symptoms

Ovarian cancer (OC) shows the highest mortality rate among gynecological malignancies and, because of the absence of specific symptoms, it is frequently diagnosed at an advanced stage, mainly due to the lack of specific and early biomarkers, such as those based on cancer molecular signature identification. Indeed, although significant progress has been made toward improving the clinical outcome of other cancers, rates of mortality for OC are essentially unchanged since 1980, suggesting the need of new approaches to identify and characterize the molecular mechanisms underlying pathogenesis and progression of these malignancies. In addition, due to the low response rate and the high frequency of resistance to current treatments, emerging therapeutic strategies against OC focus on targeting single factors and pathways specifically involved in tumor growth and metastasis. To date, loss-of-function screenings are extensively applied to identify key drug targets in cancer, seeking for more effective, disease-tailored treatments to overcome lack of response or resistance to current therapies. We review here the information relative to essential genes and functional pathways recently discovered in OC, often strictly interconnected with each other and representing promising biomarkers and molecular targets to treat these malignancies.

scholarly journals Molecular Response to PARP1 Inhibition in Ovarian Cancer Cells as Determined by Mass Spectrometry Based Proteomics

2021 ◽  
Author(s):  
Alexandra Franz ◽  
Fabian Coscia ◽  
Lea Charaoui ◽  
Ciyue Shen ◽  
Matthias Mann ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Rational Design ◽  
Molecular Mechanisms ◽  
Parp Inhibitors ◽  
Resistance Mechanisms ◽  
Ovarian Cancer Cells ◽  
Molecular Response ◽  
Growth Factor Signaling

AbstractPoly (ADP)-ribose polymerase (PARP) inhibitors have entered routine clinical practice for the treatment of high-grade serous ovarian cancer (HGSOC), yet the molecular mechanisms underlying treatment response to PARP1 inhibition (PARP1i) are not fully understood. Here, we used unbiased mass spectrometry based proteomics with data-driven protein network analysis to systematically characterize how HGSOC cells respond to PARP1i treatment. We found that PARP1i leads to pronounced proteomic changes in a diverse set of cellular processes in HGSOC cancer cells, which we confirmed in an independent perturbation dataset. We interpret decreases in the levels of the pro-proliferative transcription factors SP1 and β-catenin and in growth factor signaling as reflecting the anti-proliferative effect of PARP1i; and the strong activation of prosurvival processes NF-κB signaling and lipid metabolism as PARPi-induced adaptive resistance mechanisms. Based on these observations, we nominate several protein targets for combined therapeutic inhibition with PARP1. Our study improves the current understanding of PARP1 function, highlights the potential that the anti-tumor efficacy of PARP1i may not only rely on DNA damage repair mechanisms and informs on the rational design of PARP1i combination therapies in ovarian cancer.

scholarly journals Drug Resistance Mechanisms in Tuberculosis

2020 ◽  
Author(s):  
Lanfranco Fattorini ◽  
Angelo Iacobino ◽  
Federico Giannoni
Keyword(s):  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Drug Distribution ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Diagnostic Methods ◽  
Drug Resistant ◽  
Resistance Development ◽  
Intrinsic Drug Resistance ◽  
Incident Cases

The increased incidence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, defined as resistant to at least isoniazid and rifampin, the two highly bactericidal first-line drugs, is a major concern for tuberculosis (TB) control. The worldwide estimate of almost half a million incident cases of MDR/rifampin-resistant TB, is causing increasing concern. In this view, it is important to continuously update the knowledge on the mechanisms involved in the development of drug-resistant TB. Clinical, biological and microbiological reasons account for the generation of resistance, including: (i) nonadherence of patients to their therapy, and/or errors of physicians in therapy management, (ii) complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, resulting in resistance development, (iii) intrinsic drug resistance of tubercle bacilli, (iv) formation of non-replicating, drug-tolerant bacilli inside the granulomas, (v) development of mutations in Mtb genes, which are the most important molecular mechanisms of resistance. Here, a piece of information on the interplay of these factors is provided, to facilitate the clinical and microbiological management of drug-resistant TB at the global level, with attention also to the most recent diagnostic methods.

Molecular mechanisms of drug resistance in ovarian cancer

2018 ◽  
Vol 233 (6) ◽  
pp. 4546-4562 ◽  
Author(s):  
Leyla Norouzi-Barough ◽  
Mohammad Reza Sarookhani ◽  
Mohammadreza Sharifi ◽  
Sahar Moghbelinejad ◽  
Saranaz Jangjoo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms

scholarly journals Programmable Base Editing in Mycobacterium tuberculosis Using an Engineered CRISPR RNA-Guided Cytidine Deaminase

2021 ◽  
Vol 3 ◽  
Author(s):  
Xin-Yuan Ding ◽  
Si-Shang Li ◽  
Yi-Man Geng ◽  
Mei-Yi Yan ◽  
Guo-Bao Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Molecular Mechanisms ◽  
Cytidine Deaminase ◽  
Point Mutations ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Bacterial Physiology ◽  
Base Editing

Multidrug-resistant Mycobacterium tuberculosis (Mtb) infection seriously endangers global human health, creating an urgent need for new treatment strategies. Efficient genome editing tools can facilitate identification of key genes and pathways involved in bacterial physiology, pathogenesis, and drug resistance mechanisms, and thus contribute to the development of novel treatments for drug-resistant tuberculosis. Here, we report a two-plasmid system, MtbCBE, used to inactivate genes and introduce point mutations in Mtb. In this system, the assistant plasmid pRecX-NucSE107A expresses RecX and NucSE107A to repress RecA-dependent and NucS-dependent DNA repair systems, and the base editor plasmid pCBE expresses a fusion protein combining cytidine deaminase APOBEC1, Cas9 nickase (nCas9), and uracil DNA glycosylase inhibitor (UGI). Together, the two plasmids enabled efficient G:C to A:T base pair conversion at desired sites in the Mtb genome. The successful development of a base editing system will facilitate elucidation of the molecular mechanisms underlying Mtb pathogenesis and drug resistance and provide critical inspiration for the development of base editing tools in other microbes.

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