scholarly journals A screen to identify drug resistant variants to target-directed anti-cancer agents

10.1251/bpo63 ◽  
2003 ◽  
Vol 5 (1) ◽  
pp. 204-210 ◽  
Author(s):  
Mohammad Azam ◽  
Tal Raz ◽  
Valentina Nardi ◽  
Sarah L. Opitz ◽  
George Q. Daley
Keyword(s):  
Drug Resistant ◽  
Anti Cancer

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.

scholarly journals Enhanced drug internalization and therapeutic efficacy of PEGylated nanoparticles by one-step formulation with anti-mPEG bispecific antibody in intrinsic drug-resistant breast cancer

2019 ◽  
Vol 7 (8) ◽  
pp. 3404-3417 ◽  
Author(s):  
Yi-An Cheng ◽  
I-Ju Chen ◽  
Yu-Cheng Su ◽  
Kai-Wen Cheng ◽  
Yun-Chi Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Therapeutic Efficacy ◽  
Bispecific Antibody ◽  
Drug Resistant ◽  
Simple Method ◽  
Pegylated Nanoparticles ◽  
Anti Cancer ◽  
One Step ◽  
Tumor Specificity ◽  
Cancer Activity

One-step formulation of BsAb with PLD is a simple method to enhance tumor specificity, internalization and the anti-cancer activity.

scholarly journals Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hongbo Shen ◽  
Feifei Wang ◽  
Gucheng Zeng ◽  
Ling Shen ◽  
Han Cheng ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Proof Of Concept ◽  
Intracellular Replication ◽  
Anti Cancer ◽  
Mdr Tb ◽  
Approved Drugs ◽  
Effective Drugs ◽  
Slow Growing

Abstract While there is an urgent need to develop new and effective drugs for treatment of tuberculosis (TB) and multi-drug resistant TB (MDR-TB), repurposing FDA (U.S. Food and Drug Administration) -approved drugs for development of anti-TB agents may decrease time and effort from bench to bedside. Here, we employed host cell-based high throughput screening (HTS) assay to screen and characterize FDA-approved, off-patent library drugs for anti-Mycobacterium tuberculosis (MTB) activities. The cell-based HTS allowed us to identify an anti-cancer drug of bis-biguanide dihydrochloride (BBD) as potent anti-mycobacteria agent. Further characterization showed that BBD could inhibit intracellular and extracellular growth of M. smegmatis and slow-growing M. bovis BCG. BBD also potently inhibited replication of clinically-isolated MTB and MDR-TB strains. The proof-of-concept study showed that BBD treatment of MTB-infected mice could significantly decrease CFU counts in the lung and spleen. Notably, comparative evaluation showed that MTB CFU counts in BBD-treated mice were lower than those in rifampicin-treated mice. No apparent BBD side effects were found in BBD-treated mice. Thus, our findings support further studies to develop BBD as a new and effective drug against TB and MDR-TB.

scholarly journals Disrupters of the Thymidylate Synthase Homodimer Accelerate Its Proteasomal Degradation and Inhibit Cancer Growth.

2021 ◽  
Author(s):  
Costantino Luca ◽  
Stefania Ferrari ◽  
Matteo Santucci ◽  
Outi M. Salo-Ahen ◽  
Carosati Emanuele ◽  
...  
Keyword(s):  
Small Molecules ◽  
Thymidylate Synthase ◽  
Proteasomal Degradation ◽  
Cancer Growth ◽  
Kinetic Investigation ◽  
Drug Resistant ◽  
Intracellular Protein ◽  
Over Expression ◽  
Anti Cancer ◽  
Enhanced Expression

<p>Drugs that target human thymidylate synthase (hTS) are widely used in anti-cancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces its over-expression and the development of drug resistance. We thus pursued an alternative strategy that led to the discovery of TS-dimer disrupters that bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. We performed a structural, spectroscopic and kinetic investigation of the effects of these small molecules and<b></b>the best one, <b>E7, </b>accelerates the proteasomal degradation of hTS in cancer cells. <b>E7</b> showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, <b>E7 </b>breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.</p>

Artemisinin-acetylenedicarboxylic acid cocrystal: screening, structure determination, and physicochemical property characterisation

CrystEngComm ◽  
2022 ◽  
Author(s):  
Jay Makadia ◽  
Shadrack J Madu ◽  
Randolph Arroo ◽  
Colin Cormack Seaton ◽  
Mingzhong Li
Keyword(s):  
Physicochemical Property ◽  
Structure Determination ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Plasmodium Parasite ◽  
Anti Cancer ◽  
Acetylenedicarboxylic Acid ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
Cocrystal Screening

Artemisinin is used to treat malaria, even when caused by multi-drug resistant strains of the Plasmodium parasite; the compound also shows good promise as an anti-cancer drug. However, the usage...

Chemistry and biology of tubulysins: antimitotic tetrapeptides with activity against drug resistant cancers

2015 ◽  
Vol 32 (5) ◽  
pp. 654-662 ◽  
Author(s):  
Bryan C. Murray ◽  
Michael T. Peterson ◽  
Robert A. Fecik
Keyword(s):  
Anticancer Activity ◽  
Drug Resistant ◽  
First Report ◽  
Anti Cancer

Since their first report in 2000, tubulysins have sparked great interest for development as anti-cancer agents due to their exceptionally potent anticancer activity.

scholarly journals Sporadic ERK pulses drive non-genetic resistance in drug-adapted BRAFV600E melanoma cells

2019 ◽  
Author(s):  
Luca Gerosa ◽  
Christopher Chidley ◽  
Fabian Froehlich ◽  
Gabriela Sanchez ◽  
Sang Kyun Lim ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Tumor Regression ◽  
Mapk Pathway ◽  
Genetic Resistance ◽  
Drug Resistant ◽  
Mapk Activity ◽  
Mapk Cascades ◽  
Anti Cancer ◽  
Genetic Mechanisms ◽  
Signal Transduction Proteins

SUMMARYAnti-cancer drugs commonly target signal transduction proteins activated by mutation. In patients with BRAFV600E melanoma, small molecule RAF and MEK kinase inhibitors cause dramatic but often transient tumor regression. Emerging evidence suggests that cancer cells adapting by non-genetic mechanisms constitute a reservoir for the development of drug-resistant tumors. Here, we show that few hours after exposure to RAF/MEK inhibitors, BRAFV600E melanomas undergo adaptive changes involving disruption of negative feedback and sporadic pulsatile reactivation of the MAPK pathway, so that MAPK activity is transiently high enough in some cells to drive proliferation. Quantitative proteomics and computational modeling show that pulsatile MAPK reactivation is possible due to the co-existence in cells of two MAPK cascades: one driven by BRAFV600E that is drug-sensitive and a second driven by receptors that is drug-resistant. Paradoxically, this may account both for the frequent emergence of drug resistance and for the tolerability of RAF/MEK therapy in patients.

Industry Watch

2010 ◽  
Vol 14 (04) ◽  
pp. 23-35
Keyword(s):  
Research Collaboration ◽  
Therapeutic Protein ◽  
Influenza Vaccines ◽  
Asia Pacific ◽  
Drug Resistant ◽  
Commercial Development ◽  
Chinese University ◽  
Anti Cancer ◽  
Therapeutic Molecules ◽  
Novel Therapeutic

Integrated DNA Technologies and Glycon Partner in Australia. Phosphagenics to Develop Transdermal Insulin for Pets. NanoMaterials Technology Signs Exclusive Licensing Agreement for Hyperlipidemia-controlling Drug with Beijing Winsunny Pharmaceutical. MicuRx Pharmaceuticals,Cumencor Pharmaceuticals Partner with Pfizer to Discover and Develop Antibiotics for Drug-Resistant TBChina. Qiagen Ties up with Chinese University. Syngene to Collaborate with Endo Pharmaceuticals to Develop Anti-cancer Novel Therapeutic Molecules. Ranbaxy Collaborates With Pfenex on Development of Biosimilar Therapeutic Protein. Metabolex Initiates Research Collaboration with Takeda. AMAG, Takeda Agree to Collaborate on Feraheme Injection. Medicago Signs MOU with NITT Partners for Commercial Development of Influenza Vaccines in Japan. ICON to Open New Office in Philippines. HealthLinx Soon to Launch OvPlex in Singapore. Invida Strengthens Asia-Pacific Presence Analysis.

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