Integrins as Novel Drug Targets for Overcoming Innate Drug Resistance

Despite recent advances in cancer diagnosis, prevention, detection, as well as management, the disease is expected to be the top cause of death globally. The chemotherapy approach for cancer has become more advanced in its design, yet no medication can cure enough against all types of cancer and its stage. Thus, this review aimed to summarize a recent development of new therapeutic agents and novel drug targets for the treatment of cancer. Several obstacles stand in the way of effective cancer treatment and drug development, including inaccessibility of tumor site by appropriate drug concentration, debilitating untoward effects caused by non-selective tissue distribution of chemotherapeutic agents, and occurrence of drug resistance, which leads to cross-resistance to a variety of drugs. Resistance to treatment with anticancer drugs results from multiple factors and the most common reason for acquiring drug resistance is marking and expelling drugs that prevent cancer cells to be targeted by chemotherapeutic agents. Moreover, insensitivity to drug-induced apoptosis, alteration, and mutation of drug target and interference/change of DNA replication are other main causes of treatment failure.

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Bioorganometallic Compounds as Novel Drug Targets against Schistosomiasis in Sub-Saharan Africa: An alternative to Praziquantel?

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2022.029 ◽

2021 ◽

Author(s):

Cuma Cumisa Ndamse ◽

Priscilla Masamba ◽

Abidemi Paul Kappo

Keyword(s):

Drug Resistance ◽

Drug Targets ◽

Redox Homeostasis ◽

Organometallic Compounds ◽

Sub Saharan Africa ◽

Redox Biology ◽

Anti Cancer ◽

Sub Saharan ◽

Novel Drug ◽

Novel Drug Targets

Human schistosomiasis is a disease that mostly plagues the destitute of various tropical and sub-tropical countries, particularly in sub-Saharan Africa and South America. It has significant effects on various health and economic-related matters. Globally, the burden of schistosomiasis has been controlled with a single chemotherapeutic drug, Praziquantel, which has recently demonstrated several clinical issues, including its inability to destroy juvenile schistosome worms and drug resistance because of its extensive use. The use of organometallic moieties in biological and medicinal chemistry has developed greatly and has led to their use in various anti-cancer and anti-infectious agents. The abundance of a range of organometallic compounds that can cause damage to the parasite has received tremendous feedback, with many already at clinical trials. The distinct redox biology of the schistosome parasite is a vulnerable element to the survival of the worm and has steered attempts toward the use of redox-directed bioorganometallic compounds. Disruption of the schistosome redox homeostasis through organometallic ions provides a novel drug target that could be used in overcoming the drawbacks of the mainstream drug and one that could possibly bypass the emergence of drug resistance.

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Drug resistance mechanisms and novel drug targets for tuberculosis therapy

Journal of Genetics and Genomics ◽

10.1016/j.jgg.2016.10.002 ◽

2017 ◽

Vol 44 (1) ◽

pp. 21-37 ◽

Cited By ~ 33

Author(s):

Md Mahmudul Islam ◽

H.M. Adnan Hameed ◽

Julius Mugweru ◽

Chiranjibi Chhotaray ◽

Changwei Wang ◽

...

Keyword(s):

Drug Resistance ◽

Drug Targets ◽

Resistance Mechanisms ◽

Tuberculosis Therapy ◽

Novel Drug ◽

Novel Drug Targets

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Hepatitis C Virus and Innate Interferon Response: Pathogen Biology, Drug Resistance, Novel Drug Targets, and Therapeutic Strategies

Pathogenicity and Drug Resistance of Human Pathogens ◽

10.1007/978-981-32-9449-3_12 ◽

2019 ◽

pp. 233-249

Author(s):

Khursheed ul Islam ◽

Jawed Iqbal

Keyword(s):

Drug Resistance ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Drug Targets ◽

Therapeutic Strategies ◽

Interferon Response ◽

Novel Drug ◽

Novel Drug Targets

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Antibacterial Discovery: 21st Century Challenges

Antibiotics ◽

10.3390/antibiotics9050213 ◽

2020 ◽

Vol 9 (5) ◽

pp. 213 ◽

Cited By ~ 2

Author(s):

Paul S. Hoffman

Keyword(s):

Drug Resistance ◽

21St Century ◽

Drug Targets ◽

Anaerobic Bacteria ◽

Multidrug Resistant ◽

Wide Range ◽

New Chemical Entities ◽

Antibiotic Discovery ◽

Novel Drug ◽

Novel Drug Targets

It has been nearly 50 years since the golden age of antibiotic discovery (1945–1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.

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