Breaking News
May 26, 2018 - Lifetime risks of developing Alzheimer’s dementia vary by age, gender
May 26, 2018 - Researchers find novel ways to improve participation in clinical research
May 26, 2018 - Researchers develop methods for measuring free-base nicotine levels in e-cigarettes
May 26, 2018 - AHA: Preterm Birth Could Warn of Mom’s Future Heart Risks
May 26, 2018 - Some calories more harmful than others
May 26, 2018 - Study links cell size with commitment to division
May 26, 2018 - Researchers develop new, rapid blood test to detect liver damage
May 26, 2018 - Researchers discover cascade of immune processes linked to poor outcomes in aggressive breast cancer
May 26, 2018 - New research will use mathematics to solve mysteries in cell biology
May 26, 2018 - Mice remain slim on burger diet
May 26, 2018 - BMC receives $13.5 million award to test methods for delivering childhood anxiety treatment
May 26, 2018 - ‘Right to Try Act’ will not benefit terminally-ill patients
May 26, 2018 - Study reveals novel statistical algorithm to identify potential disease genes
May 26, 2018 - Two genes play vital roles in malignant brain cancer
May 26, 2018 - Study explores link between groundwater lithium and diagnoses of bipolar disorder, dementia
May 26, 2018 - Researchers reveal stimulatory effects of myelin on young neural cells
May 26, 2018 - Small part of cellular protein that helps form long-term memories also drives neurodegeneration
May 26, 2018 - Four-legged friends can have heart issues, too
May 26, 2018 - Scientists create small, self-contained spaces inside mammalian cells
May 26, 2018 - Better Social Support Network Protects Black Men Against HIV
May 26, 2018 - National Heart, Lung, and Blood Institute (NHLBI)
May 26, 2018 - Burnout, depression can affect ophthalmology residents, study finds
May 26, 2018 - Latinos and African Americans more likely to experience serious depression than Whites
May 26, 2018 - Data from past epidemic could help improve response to future Ebola outbreaks
May 26, 2018 - Researchers provide insight into how the memory molecule limits brain plasticity
May 26, 2018 - OSU biologist describes ‘restoration ecology’ approach toward patient health
May 26, 2018 - New approach to study brown fat could aid in finding treatments for obesity
May 26, 2018 - Could More Fish in the Diet Boost Sex Lives and Fertility?
May 26, 2018 - NTU Singapore and SERI invent new scope to diagnose glaucoma
May 26, 2018 - Cancer cells co-opt pain-sensing ‘neural channel’ to increase tolerance against oxidative stress
May 26, 2018 - Study uncovers why pesticide exposure increases Parkinson’s disease risk in some people
May 26, 2018 - Study finds link between lead exposure and fertility rates
May 26, 2018 - Delivery of standardized diabetes care could help achieve equitable health outcomes for all patients
May 26, 2018 - FDA authorizes marketing of OsteoDetect software for detecting wrist fractures
May 26, 2018 - Children and adolescents growing up in extreme societal conditions more likely to resort to violence
May 26, 2018 - New study puts forth most comprehensive tree of life for malaria parasites
May 26, 2018 - UVA researchers establish new guidelines for explorers of the submicroscopic world inside us
May 26, 2018 - Princeton Instruments and C-SOPS announce collaboration on innovative pharmaceutical technology
May 26, 2018 - New research shows why babies need to move in the womb
May 26, 2018 - UK steps forward to tackle global antimicrobial resistance
May 26, 2018 - CRISPR-Cas9-based strategy allows researchers to precisely alter hundreds of different genes
May 26, 2018 - Novoheart announces next generation of ‘Human heart-in-a-jar’ technology for advanced drug discovery
May 26, 2018 - UT Southwestern-led researchers find new way to determine prognosis of invasive kidney cancer
May 26, 2018 - Researchers develop film to prevent bacteria from growing on dental retainers and aligners
May 26, 2018 - Mobile health intervention for people with serious mental illness as effective as clinic-based treatment
May 26, 2018 - Vaginal estradiol tablets outperform moisturizers when treating vulvovaginal problems
May 26, 2018 - Researchers call for new genetic tests for congenital diseases
May 26, 2018 - KHN’s ‘What the Health?’ Campaign promises kept, plus ‘nerd reports’
May 26, 2018 - AARDA collaborates with Allegheny Health Network and new AHN Autoimmunity Institute
May 26, 2018 - Lung-on-a-chip technology could streamline drug-testing for pulmonary fibrosis
May 26, 2018 - Researchers work together to solve mystery of motor neuron death in ALS patients
May 26, 2018 - Study finds early antibiotic initiation for majority of premature infants
May 26, 2018 - New environmental monitoring project finds increased numbers of deer ticks in Southern Indiana
May 26, 2018 - Pediatricians Should Advocate for Life Support Training
May 26, 2018 - Cannabidiol significantly reduces seizures in patients with severe form of epilepsy
May 26, 2018 - Allergies can have serious, far-reaching consequences on adolescents
May 26, 2018 - Scientists develop lab-based system to study mechanisms of common liver disease
May 25, 2018 - New guidelines may help pathologists to more accurately classify and diagnose invasive melanoma
May 25, 2018 - Immune cells promote lung cancer metastases by forming clots in tumors, study finds
May 25, 2018 - Can Excess Weight in Toddlers Cause Brain Drain?
May 25, 2018 - Studying insight
May 25, 2018 - Researchers reveal potent new mechanism of action for treatment of IBD
May 25, 2018 - Study shows lack of follow-up care for patients with concussion
May 25, 2018 - Study establishes the importance of haploid cells
May 25, 2018 - Coveted BMJ award bestowed on The Clatterbridge Cancer Center
May 25, 2018 - AACN outlines evidence-based protocols and clinical strategies to manage alarms
May 25, 2018 - Origami inspires researchers to develop new solution for tissue regeneration
May 25, 2018 - Melorheostosis – Genetics Home Reference
May 25, 2018 - Non-addictive pain medication changing therapy for substance use disorders
May 25, 2018 - Delayed lactate measurements in sepsis patients increase risk of in-hospital death
May 25, 2018 - Researchers identify novel epigenetic mutations as cause of neurodevelopmental, congenital disorders
May 25, 2018 - UD researchers examine connection between DNA replication in HPV and cancer
May 25, 2018 - Researchers identify neurons that play key role in aggressive behavior
May 25, 2018 - Snail’s eye inspires new type of RIOCATH urinary catheter
May 25, 2018 - Russian researchers develop high-tech device-transformer for ultrasound examination
May 25, 2018 - Researchers discover unexpected chemosensor pathway for predator odor-evoked innate fear behaviors
May 25, 2018 - Researchers build 3-D printer that offers sweet solution to making detailed structures
May 25, 2018 - Nearly one in three people know someone addicted to opioids
May 25, 2018 - Research suggests link between faulty gene, alcohol, and heart failure
May 25, 2018 - New findings could help fine-tune treatment for cancer patients
UT Southwestern researchers identify 170 potential therapeutic targets for lung cancer

UT Southwestern researchers identify 170 potential therapeutic targets for lung cancer

image_pdfDownload PDFimage_print

After testing more than 200,000 chemical compounds, UT Southwestern’s Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

The 5-year project set out to identify new therapeutic targets for non-small cell lung cancer as well as potential drugs for these targets – a significant step forward toward personalizing cancer care.

“For the large majority of compounds, we identified a predictive biomarker – a feature that allows the development of ‘precision medicine,’ or individualized treatment for each patient, which is a major goal of the Simmons Cancer Center,” said Dr. John Minna, Director of the Hamon Center for Therapeutic Oncology Research at UT Southwestern Medical Center.

Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute. Non-small cell lung cancer, the type of cancer studied in this research, comprises approximately 85 percent of all lung cancers. In 2017, lung cancer caused 26 percent of all cancer deaths.​

Using UT Southwestern’s unique lung cancer cell library that is now the world’s largest, the researchers searched for compounds that would kill cancer cells but not harm normal lung cells.

“We began an ambitious project with the goal of identifying ‘therapeutic triads’: chemicals that kill cancer cells, biomarkers that predict who would respond, and the therapeutic targets on which those active chemicals work,” said Dr. Minna, Professor of Internal Medicine and Pharmacology who holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology.

Continuing to uncover the mechanism of action for the majority of the 170 chemicals will be a key focus of future research. Follow-up work will also include testing the chemicals on other types of cancer. Preliminary work shows some of the compounds are likely effective against certain breast and ovarian cancers as well.

Results of this complex project, led by Dr. Michael White, former Professor of Cell Biology and now Vice President for Oncology Drug Development at Pfizer Inc., involved members of the Harold C. Simmons Comprehensive Cancer Center and the Departments of Cell Biology, Biochemistry, Pharmacology, and Internal Medicine, and appear in the journal Cell.

Dr. Minna, along with his research partner Dr. Adi Gazdar, Professor of Pathology and with the Hamon Center for Therapeutic Oncology, have carefully developed and curated a collection of lung cancer cell lines since the 1970s that is now recognized as the world’s largest – and upon which this research was based. Dr. Minna was named a “Giant of Cancer Care” in 2015 in recognition of this work developing lung cancer cell lines.

What made this work unusual was that they began with the chemical compounds.

“Almost all cancer research is gene-first, or target-first. We began with the potential drugs,” said Dr. Michael Roth, Professor of Biochemistry and a member of the Simmons Cancer Center.

Using UT Southwestern’s High-Throughput Screening Core Facility, the team of scientists began by testing 200,000 chemicals against 12 lung cancer cell lines.

“The initial screen gave us 15,000 chemical ‘hits,’ way too many to work with in detail, but with repeat testing we eventually narrowed the number down to 170. We called this the UT Southwestern ‘Precision Oncology Probe Set,’ or POPS,” said Dr. Bruce Posner, Professor of Biochemistry and Director of the High-Throughput center.

The set of 170 chemical compounds was then tested across 100 lung cancer lines.

At the same time, researchers conducted in-depth molecular analyses of the lung cancer lines, including identification of genome mutations and protein expression. This information, paired with whether or not an individual cancer cell line was sensitive to a particular chemical, allowed the researchers to develop a set of biomarkers – indicators that could be used to determine if a particular cancer will respond to one of the 170 chemical compounds.

The final step of the study was determining how the drugs acts on the cancer. “We scoured existing knowledge and were able to come up with the target for several examples to complete the third leg of the triad,” said Dr. Roth, who holds the Diane and Hal Brierley Distinguished Chair in Biomedical Research at UT Southwestern, which is recognizing its 75th anniversary this year.

Source:

http://www.utsouthwestern.edu/newsroom/articles/year-2018/170-lung-cancer-drugs.html

Tagged with:

About author

Related Articles