Candidate Drug Kills CRCs with Mutated Tumor Suppressor Gene
|
By LabMedica International staff writers Posted on 04 Nov 2016 |
|
Image: The protein produced by the adenomatous polyposis coli (APC) tumor suppressor gene (Photo courtesy of Wikimedia Commons).
A candidate small molecule drug for treatment of colorectal cancer acts by blocking cholesterol biosynthesis in a subset of tumor cells that carry a mutated version of a gene that normally suppresses tumor formation.
Mutations in the adenomatous polyposis coli (APC) gene are common in colorectal cancer (CRC) - they are found in more than 80% of colon tumors - and more than 90% of those mutations generate stable truncated gene products.
To identify candidate drugs capable of killing CRC cells with mutated APC, investigators at the University of Texas Southwest Medical Center (Dallas, USA) screened more than 200,000 compounds against a panel of normal human colonic epithelial cells (HCECs) and a series of oncogenically progressed HCECs containing a truncated APC protein.
They reported in the October 19, 2016, online edition of the journal Science Translational Medicine that a small molecule, TASIN-1 (truncated APC selective inhibitor-1), specifically killed cells with APC truncations but spared normal and cancer cells with wild-type APC. TASIN-1 exerted its cytotoxic effects through inhibition of cholesterol biosynthesis.
In vivo administration of TASIN-1 inhibited tumor growth of CRC cells with truncated APC but not APC wild-type CRC cells in xenograft models and in a genetically engineered CRC mouse model with minimal toxicity.
"Even though such mutations are common in colorectal cancer, there are currently not any therapeutics that directly target these types of mutations, so this represents fresh avenues to approach," said senior author Dr. Jerry W. Shay, professor of cell biology at the University of Texas Southwest Medical Center. "Our latest finding confirms that targeting TASINs is a viable approach. Considering the high prevalence of APC mutations in colon cancer patients, targeting truncated APC could be an effective therapeutic strategy for prevention and intervention of colorectal cancer and could potentially be used as a marker for stratifying patients in future personalized medicine clinical trials."
Related Links:
University of Texas Southwest Medical Center
Mutations in the adenomatous polyposis coli (APC) gene are common in colorectal cancer (CRC) - they are found in more than 80% of colon tumors - and more than 90% of those mutations generate stable truncated gene products.
To identify candidate drugs capable of killing CRC cells with mutated APC, investigators at the University of Texas Southwest Medical Center (Dallas, USA) screened more than 200,000 compounds against a panel of normal human colonic epithelial cells (HCECs) and a series of oncogenically progressed HCECs containing a truncated APC protein.
They reported in the October 19, 2016, online edition of the journal Science Translational Medicine that a small molecule, TASIN-1 (truncated APC selective inhibitor-1), specifically killed cells with APC truncations but spared normal and cancer cells with wild-type APC. TASIN-1 exerted its cytotoxic effects through inhibition of cholesterol biosynthesis.
In vivo administration of TASIN-1 inhibited tumor growth of CRC cells with truncated APC but not APC wild-type CRC cells in xenograft models and in a genetically engineered CRC mouse model with minimal toxicity.
"Even though such mutations are common in colorectal cancer, there are currently not any therapeutics that directly target these types of mutations, so this represents fresh avenues to approach," said senior author Dr. Jerry W. Shay, professor of cell biology at the University of Texas Southwest Medical Center. "Our latest finding confirms that targeting TASINs is a viable approach. Considering the high prevalence of APC mutations in colon cancer patients, targeting truncated APC could be an effective therapeutic strategy for prevention and intervention of colorectal cancer and could potentially be used as a marker for stratifying patients in future personalized medicine clinical trials."
Related Links:
University of Texas Southwest Medical Center
Platinum Member
Automated Coagulation Analyzer
Hemolumi H6
New
Alzheimer's Disease Biomarker Assay
Elecsys Phospho-Tau (217P) Plasma
Gold Member
Neonatal Heel Incision Device
Tenderfoot
Latest BioResearch News
- Cancer DNA Trapping Mechanism Reveals Potential Target for Future Therapies
- Blood Antibody Signals May Offer Clues to the Origins of Childhood Cancer
- Genetic Study Links Inherited Blindness to Gene Tied to Rare Metabolic Disorder
- Population-Scale Proteomics Study Identifies New Genetic-Protein Links
- Circulating Tumor DNA Helps Identify Targets for Personalized Immunotherapy
- Researchers Classify 108 Lysosomal Disorders in Updated Diagnostic Framework
- New Autoantibody Target Identified in Neuromyelitis Optica Spectrum Disorder
- New Immune Target Could Support More Precise High Blood Pressure Treatment
- New Gene-Disease Link May Help Diagnose Rare Neurodevelopmental Disorders
- Researchers Identify Shared Molecular Networks Behind Fatigue-Related Illnesses
- Blood Metabolite Signature Predicts ALS Progression and Points to Treatment Strategy
- Whole-Blood Extracellular Vesicle Analysis Captures Molecular Signals Missed by Plasma Testing
- Age-Related Genomic Differences Could Refine Treatment Decisions in Lung Cancer
- Computational Tool Identifies Central Asthma Genes for Target Discovery
- Molecular Pathway Reveals Driver of Triple-Negative Breast Cancer Spread
- D-Serine May Predict Immune Checkpoint Therapy Resistance in Gastric Cancer
Channels
Clinical Chemistry
view channel
New One-Step Syphilis Test Could Enable Earlier Detection and Faster Treatment
Syphilis can be difficult to diagnose because its symptoms may resemble other diseases and appear and disappear without treatment. Undetected infection can continue causing harm, spread to partners and... Read more
Multimodal Clinical Data Models Predict Cachexia Risk Across Cancers
Cancer cachexia is a severe wasting syndrome that affects roughly half of patients with cancer and cannot be reversed simply by increasing food intake. It can reduce treatment tolerance, impair quality... Read more
Molecular Diagnostics
view channel
RNA-Based Test Predicts Immunotherapy Response in Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) represents the largest U.S. patient population eligible for immune checkpoint inhibitor therapy. Treatment selection often relies on PD-L1 expression, but a single protein... Read more
Modeling Study Shows Blood-Based CRC Screening Could Prevent More Deaths Than Stool Tests
Colorectal cancer (CRC) screening depends on patient participation and completion of follow-up colonoscopy after an abnormal noninvasive result. Access barriers can make both steps difficult, particularly... Read more
Hematology
view channel
New Myelofibrosis Guidelines Recommend Expanded Genetic Testing at Diagnosis
Myelofibrosis is a rare, life-threatening blood cancer affecting up to six per 100,000 people. The disease causes scarring in the bone marrow, limiting the production of healthy blood cells and potentially... Read more
Handheld Point-of-Care Test Aims to Enable Rapid Coagulation Assessment in Trauma
Severe blood loss and inadequate tissue oxygenation are leading causes of preventable death after traumatic injury. Blood products are essential in trauma care, but cold-chain storage, short shelf life,... Read more
Immunology
view channel
Immune Profiling Identifies Early Maternal Autoantibodies Linked to Preterm Birth Risk
A typical pregnancy lasts about 40 weeks, but labor begins prematurely in roughly one in 10 pregnancies. Preterm birth is the leading cause of newborn death worldwide, yet its underlying causes and which... Read more
Longitudinal Blood Testing Reveals Changes in Allergen Sensitization During Childhood
Food allergy is a major childhood health concern, and distinguishing persistent risk from transient sensitization can guide clinical decisions. Specific IgE antibodies may be detectable even when a child... Read more
Microbiology
view channel
Rapid Host-Response Test Aims to Predict Corticosteroid Benefit in Sepsis
Sepsis and severe infections are difficult to treat because patients with similar clinical presentations may have very different underlying immune responses. Corticosteroids are commonly used in severe... Read more
Oral and Lung Microbiome Changes Linked to Severe Long Covid Symptoms
Long Covid can involve persistent respiratory, cognitive, and gastrointestinal symptoms after acute infection, creating a difficult diagnostic and management challenge. Because COVID-19 initially affects... Read more
Pathology
view channel
Molecular Testing Refines Barrett’s Esophagus Progression Risk Beyond Biopsy Findings
Barrett’s esophagus is a precancerous condition associated with increased risk of esophageal adenocarcinoma. Routine endoscopic biopsy findings guide surveillance and therapy, but histopathology may not... Read more
Updated Digital Pathology Platform Expands AI Integration for Cancer Diagnosis
Digital pathology is reshaping how laboratories manage case review, image analysis, and collaboration. As diagnostic workflows become more complex, pathology teams need platforms that can support digital... Read more
Technology
view channel
Laser-Based Swab Analysis Shows Promise for Detecting Disease-Linked Odor Patterns
Disease-related changes in volatile organic compounds can alter body odor, producing measurable patterns in exhaled breath and bodily fluids. Current analytical methods can be complex, time-consuming,... Read more
Laser-Enhanced Assay Boosts Sensitivity for Colorectal Cancer Biomarker Detection
Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. Early detection remains critical, but cancer biomarkers can produce only faint... Read more
Industry
view channel
Global TB Summit Connects Diagnostic Testing With Prevention and Clinical Care
Tuberculosis remains a major global infectious disease challenge despite declining deaths. In 2024, an estimated 10.7 million people worldwide developed the disease and nearly 1.2 million died from it.... Read more
