OCT 30, 2018 01:24 PM PDT

Re-sensitizing Drug-resistant Human Tumor Cells

WRITTEN BY: Nouran Amin

Understanding how cancer cells avoid death despite their DNA being damaged will create new strategies to enhance cancer cell killing through chemotherapy treatment. Even though the most widely used drugs are DNA-damaging agents (DDAs), their therapeutic success has been often halted by drug resistance. Addressing the challenges of drug resistance is crucial in the field of clinical cancer treatments.

Watch the short video below to learn more about drug-resistant cancer:

Now, a recent study published in the Nature Structural and Molecular Biology discusses a new way of re-sensitizing drug-resistant human tumor cells to the potency of DDAs and paving the way to new strategies to overcome chemotherapeutic drug resistance.

The researchers found that protein, called Schlafen 11, inhibits the production of two other proteins ATM and ATR that are found in tumor cells. "We found that if you expose cells that have Schlafen 11 to DNA damaging agents, the Schlafen 11 protein gets activated and suppresses the synthesis of ATM and ATR -- that's essentially what kills the tumor cells," explains Professor Michael David, a professor in the Biological Sciences Section of Molecular Biology and UC San Diego Moores Cancer Center. "In cells that do not express Schlafen 11, you do not get this downregulation of ATM/ATR and that essentially allows the tumor cells to survive."

Credit: Manqing Li, Michael David Lab, UC San Diego

Image: “Pancreatic cancer cells deficient in the expression of the human gene known as Schlafen 11 and resistant to chemotherapy (left panels) were re-sensitized to chemotherapeutic treatment (middle and right panels) by inhibiting the expression of the transfer RNA known as tRNA-Leu-TAA through specially designed antisense oligonucleotides.”- ScienceDaily

Digging deeper into the mechanism of Schlafen 11 works on a molecular level, the researchers discovered that most of the genes involved in DNA damage repair pathways will display a similar skewing of their transfer RNA seen in HIV, specifically towards tRNA-Leu-TAA—prompting a new tecnhique to re-sensitize Schlafen 11-deficient tumor cells to drugs via the targeting of tRNA-Leu-TAA.

Such intervention may influence the entire DNA damage repair pathway -- including ATM and ATR – to not just inhibit the function of one specific component at a time. "These results suggest two ways to enhance the killing of cancer cells by DNA-damaging drugs by adding 1) ATR inhibitors or 2) tRNA inhibitors," said study coauthor Jean Wang, professor emeritus in UC San Diego's School of Medicine. "The paper is also of significance to the basic research on DNA damage response because it shows for the first time that regulation of tRNAs determines when a damaged cell will survive or die."

Despite being relevant to DNA damage and cancer, the research holds applications in immunology and virology, particularly in HIV treatments, because of the fundamental mechanisms behind Schlafen 11.

Source: Nature Structural & Molecular Biology, Science Daily

About the Author
  • Nouran enjoys writing on various topics including science & medicine, global health, and conservation biology. She hopes through her writing she can make science more engaging and communicable to the general public.
You May Also Like
OCT 13, 2019
Cancer
OCT 13, 2019
Using VR to Design Medicine
Being able to visualize and precisely understand molecular shapes is a key factor in drug design. Over the years, to envision and better understand molecul...
OCT 13, 2019
Drug Discovery & Development
OCT 13, 2019
Promising Drug Encourages Survival in Pancreatic Cancer
Building on almost 20 years of research, a phase 1 clinical trial drug for pancreatic cancer, named ‘AZD1775’, shows promising initial results ...
OCT 13, 2019
Technology
OCT 13, 2019
Computer Model Advances New Therapeutics for Sickle Cell Anemia
A team of Brown University researchers has developed a new computer model that simulates the way red blood cells become misshapen by sickle cell anemia. A ...
OCT 13, 2019
Drug Discovery & Development
OCT 13, 2019
Leukemia Drug Effective for Treating Childhood Brain Cancer
Scientists at the University of California-San Diego have found that a chronic myeloid leukemia drug was found to treat medulloblastoma in mouse models mor...
OCT 13, 2019
Genetics & Genomics
OCT 13, 2019
Non-Invasive Gene Therapy Holds Promise for Treating Blindness
Researchers at John Hopkins Medicine have found a way to deliver sight-saving gene therapy to the retina. Having already shown success in treating rates, p...
OCT 13, 2019
Drug Discovery & Development
OCT 13, 2019
Tailor-made Drug for Girl with Rare Genetic Disease
Researchers have used personalized medicine to develop a tailor-made genetic treatment for a girl diagnosed with a rare genetic disease known as Batten dis...
Loading Comments...