Cancer therapy is often hampered by the rapid emergence of drug resistance. Drug-resistant cellular models are essential for understanding the drug resistance and developing new therapeutics. The low efficiency and long time required in creating these models are major obstacles hindering drug resistance research and drug screening. Herein, we report an approach that can accelerate (shortening the time from years to 3 weeks) the establishment of cancer cell line-based, inheritable drug resistance models by specific knockout of MED12 gene using CRISPR/Cas9 system. The resultant MED12 A375 (melanoma) cell line was resistant to inhibitors of B-Raf proto-oncogene, serine/threonine kinase (BRAF), whereas the resultant MED12 PC9 (non-small cell lung cancer) cell line was resistant to inhibitors of epidermal growth factor receptor (EGFR). Evaluation of anti-cancer drugs and their combinations shows that certain combinations of BRAF inhibitors and TGF-β receptor (TGF- βR) inhibitors are active in suppressing the growth of MED12 A375 cells, and a few combinations of EGFR inhibitors and TGF-βR inhibitors were active in suppressing the growth of MED12 PC9 cells. The drug-resistant models will be useful in screening novel drugs and drug combinations for multi-drug-resistant cancer therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.scib.2018.09.024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cystine-Modified Lignin-Copper Coordination Nanocarriers Improve the Therapeutic Efficacy of Tyrosine Kinase Inhibition via Cuproptosis.
ACS Appl Mater Interfaces
January 2025
Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong 510060, P. R. China.
The clinical application of tyrosine kinase inhibitors (TKIs) is rapidly growing and has emerged as a cornerstone in the treatment of both solid tumors and hematologic malignancies. However, resistance to TKI targets and disease progression remain inevitable. Nanocarrier-mediated delivery has emerged as a promising strategy to overcome the limitations of the TKI application.
View Article and Find Full Text PDFInnovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy.
ACS Nano
January 2025
Institute of Nanobiomaterials and Immunology & Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Life Sciences, Taizhou University, Zhejiang Taizhou 318000, China.
Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including , , and , along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME).
View Article and Find Full Text PDFChangeover method for biosafety cabinets using ozone gas.
PLoS One
January 2025
Center for Stem Cell and Regenerative Medicine, Institute of Science Tokyo, Bunkyo-ku, Tokyo, Japan.
This study evaluated the effectiveness of a biosafety cabinet equipped with an ozone generator, particularly during the transition periods between the production of cell products. As living cell products cannot undergo sterilization, maintaining an aseptic manufacturing environment is paramount. Raw materials, often derived from human tissues, are frequently contaminated with various resident bacteria, necessitating environmental resets after each process.
View Article and Find Full Text PDFThe neurohormone tyramine stimulates the secretion of an insulin-like peptide from the Caenorhabditis elegans intestine to modulate the systemic stress response.
PLoS Biol
January 2025
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) CCT UNS-CONICET, Bahía Blanca, Argentina.
The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood.
View Article and Find Full Text PDFImproved insulin sensitivity and reproductive profile in overweight/obese PCOS patients undergoing integrative treatment with carnitines, L-arginine, L-cysteine and myo-inositol.
Gynecol Endocrinol
December 2025
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.
Objective: To evaluate the effects of a combination of carnitines, L-arginine, L-cysteine and myo-inositol on metabolic and reproductive parameters in PCOS overweight/obese patients.
Methods: This was a retrospective study analyzing information of a group of PCOS ( = 25) overweight/obesity patients, not requiring hormonal treatment, selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Modena, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of a daily oral complementary treatment with L-carnitine (500 mg), acetyl-L-carnitine (250 mg), L-arginine (500 mg), L-cysteine (100 mg) and myo-inositol (1 gr).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!