Genetic Test Determines Patients Sensitivity to Cancer Drug
By LabMedica International staff writers Posted on 12 Jan 2017 |
Image: The BD LSR II flow cytometry analyzer (Photo courtesy of BD Bioscience).
The identification of genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Testing for a gene commonly mutated in ovarian cancers could pick out patients who will respond well to a promising new class of cancer drugs.
Oncogene activation can induce replication stress and reliance upon an Ataxia-Telangiectasia protein (ATR) checkpoint function and this provides one rationale for the use of small molecule ATR inhibitors (ATRi) as cancer therapeutics.
A team of scientists at the Institute of Cancer Research have demonstrated that defects in AT-Rich Interaction Domain 1A (ARID1A) sensitize tumor cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo. The team used a multiplicity of techniques including cell lines, ribonucleic acid screening, Western blots and antibodies, cellular viability assays, and immunofluorescence using a confocal microscope. Some samples were analyzed on a BD LSR II flow cytometer.
The scientists found that found that ATR inhibitors stopped cancer cells with ARID1A mutations from growing, both in culture dishes and in mice. They also found that switching off the ARID1A gene in breast and bowel cancer cells greatly increased their sensitivity to ATR inhibitors. They found the treatment killed cancer cells with ARID1A mutations through a process called 'synthetic lethality'. Patients on clinical trials of ATR inhibitors could now start to be tested for ARID1A mutations in their tumors in order to assess whether those with the genetic defects are particularly likely to benefit.
Justine Alford, PhD, a senior science information officer for Cancer research UK, said, “By identifying a potential way to exploit a specific genetic vulnerability in cancer this study could point the way to tailoring treatments to each patient, helping to make them kinder and more effective. The next steps will be to better understand the effects of targeting this weakness, and to find out whether this promising strategy will work in people.” The study was published on December 13, 2016, in the journal Nature Communications.
Oncogene activation can induce replication stress and reliance upon an Ataxia-Telangiectasia protein (ATR) checkpoint function and this provides one rationale for the use of small molecule ATR inhibitors (ATRi) as cancer therapeutics.
A team of scientists at the Institute of Cancer Research have demonstrated that defects in AT-Rich Interaction Domain 1A (ARID1A) sensitize tumor cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo. The team used a multiplicity of techniques including cell lines, ribonucleic acid screening, Western blots and antibodies, cellular viability assays, and immunofluorescence using a confocal microscope. Some samples were analyzed on a BD LSR II flow cytometer.
The scientists found that found that ATR inhibitors stopped cancer cells with ARID1A mutations from growing, both in culture dishes and in mice. They also found that switching off the ARID1A gene in breast and bowel cancer cells greatly increased their sensitivity to ATR inhibitors. They found the treatment killed cancer cells with ARID1A mutations through a process called 'synthetic lethality'. Patients on clinical trials of ATR inhibitors could now start to be tested for ARID1A mutations in their tumors in order to assess whether those with the genetic defects are particularly likely to benefit.
Justine Alford, PhD, a senior science information officer for Cancer research UK, said, “By identifying a potential way to exploit a specific genetic vulnerability in cancer this study could point the way to tailoring treatments to each patient, helping to make them kinder and more effective. The next steps will be to better understand the effects of targeting this weakness, and to find out whether this promising strategy will work in people.” The study was published on December 13, 2016, in the journal Nature Communications.
Latest Molecular Diagnostics News
- Novel Biomarkers to Improve Diagnosis of Renal Cell Carcinoma Subtypes
- RNA-Powered Molecular Test to Help Combat Early-Age Onset Colorectal Cancer
- Advanced Blood Test to Spot Alzheimer's Before Progression to Dementia
- Multi-Omic Noninvasive Urine-Based DNA Test to Improve Bladder Cancer Detection
- First of Its Kind NGS Assay for Precise Detection of BCR::ABL1 Fusion Gene to Enable Personalized Leukemia Treatment
- Urine Test to Revolutionize Lyme Disease Testing
- Simple Blood Test Could Enable First Quantitative Assessments for Future Cerebrovascular Disease
- New Genetic Testing Procedure Combined With Ultrasound Detects High Cardiovascular Risk
- Blood Samples Enhance B-Cell Lymphoma Diagnostics and Prognosis
- Blood Test Predicts Knee Osteoarthritis Eight Years Before Signs Appears On X-Rays
- Blood Test Accurately Predicts Lung Cancer Risk and Reduces Need for Scans
- Unique Autoantibody Signature to Help Diagnose Multiple Sclerosis Years before Symptom Onset
- Blood Test Could Detect HPV-Associated Cancers 10 Years before Clinical Diagnosis
- Low-Cost Point-Of-Care Diagnostic to Expand Access to STI Testing
- 18-Gene Urine Test for Prostate Cancer to Help Avoid Unnecessary Biopsies
- Urine-Based Test Detects Head and Neck Cancer