Breaking News
February 20, 2019 - Study sheds new light on how antibiotic resistance genes are transferred between bacteria
February 20, 2019 - Chronic Wasting Disease may soon spread to humans, warns CDC
February 20, 2019 - Scientists identify new genetic causes linked to abnormal pregnancies and miscarriages
February 20, 2019 - Using LyoSpeed technology to avoid residual solvent when drying HPLC fractions
February 20, 2019 - New screening tool more likely to identify sexual and labor exploitation of youth
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
February 20, 2019 - Physicians graduated outside the U.S. offer better care for Medicare patients with complex needs
February 20, 2019 - FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection
February 20, 2019 - Study identifies brain cells that modulate behavioral response to threats
February 20, 2019 - Researchers take closer look at how viruses bind cells and cause infection
February 20, 2019 - Newly developed gene therapy helps decelerate aging process
February 20, 2019 - Study suggests new treatment strategy for deadly brain cancer
February 20, 2019 - Scientists develop unique hybrid implant that imitates bone structure
February 20, 2019 - Push-ups can be tailored to meet specific needs of individuals
February 20, 2019 - Early-career job loss has long term health implications
February 20, 2019 - CVD Does Not Modify Depression-Mortality Link in Elderly
February 20, 2019 - Electrical activity early in fruit flies’ brain development could shed light on how neurons wire the brain
February 20, 2019 - Machine learning technique helps predict which asthma patients respond to corticosteroid therapy
February 20, 2019 - Self-reported sleep duration is a useful tool to measure sleep in children, study suggests
February 20, 2019 - T-cells play key role in how the body fights follicular lymphoma
February 20, 2019 - Study shows how 3D organization of genetic material helps perpetuate the species
February 20, 2019 - Researchers engineer stem cell with ‘suicide genes’ to induce cell death in all but beta cells
February 20, 2019 - Study reveals major sex differences in management of cardiovascular risk factors among U.S. adults
February 20, 2019 - Health Tip: Get Your Child to School on Time
February 20, 2019 - Shortcut strategy for screening compounds with clinical potentials for drug development
February 20, 2019 - Common acid reflux drugs tied to elevated risk for kidney disease
February 20, 2019 - Microbiome could be culprit when good drugs do harm
February 20, 2019 - Prenatal exposure to forest fires causes stunted growth in children
February 20, 2019 - Gene therapy restores hearing in mice with congenital genetic deafness
February 20, 2019 - First molecular test predicts treatment response for kidney cancer
February 20, 2019 - New method for improved visualization of single-cell RNA- sequencing data
February 20, 2019 - Researchers capture altered brain activity patterns of Parkinson’s in mice
February 20, 2019 - A possible blood test for detecting Alzheimer’s disease before symptoms show
February 20, 2019 - Primary care physicians associated with longevity, new research finds
February 19, 2019 - New study identifies many key lessons to establish sanctioned safe consumption sites
February 19, 2019 - Single CRISPR treatment can safely and stably correct genetic disease
February 19, 2019 - Multinational initiative to study familial primary distal renal tubular acidosis
February 19, 2019 - Breakthrough study highlights the promise of cell therapies for muscular dystrophy
February 19, 2019 - Subsymptom Threshold Exercise Speeds Concussion Recovery
February 19, 2019 - Midline venous catheters – infants: MedlinePlus Medical Encyclopedia
February 19, 2019 - Searching for side effects
February 19, 2019 - Humanity is all right, probably, although human extinction remains quite possible, researcher says
February 19, 2019 - Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows
February 19, 2019 - Anti-cancer immunotherapy could be used to fight HIV
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
February 19, 2019 - COPD patients need more support when understanding new chest symptoms
February 19, 2019 - Using light-based method for production of pharmaceutical molecules
February 19, 2019 - Scientists find link between inflammation and cancer
February 19, 2019 - The High Cost Of Sex: Insurers Often Don’t Pay For Drugs To Treat Problems
February 19, 2019 - Hearing impairment associated with accelerated cognitive decline with age
February 19, 2019 - Researchers identify multiple genetic variants associated with body fat distribution
February 19, 2019 - Influenza and common cold are completely different diseases, study shows
February 19, 2019 - Scientists untangle how microbes manufacture key antibiotic compound
February 19, 2019 - Greater primary care physician supply associated with longer life spans
February 19, 2019 - HIV-1 protein suppresses immune response more broadly than thought
February 19, 2019 - Brain imaging indicates potential success of drug therapy in depressive patients
February 19, 2019 - For 2020 Dem Hopefuls, ‘Medicare-For-All’ Is A Defining Issue, However They Define It
February 19, 2019 - Specialized lung cells appear in the developing fetus much earlier than previously thought
February 19, 2019 - KU professor discusses promise of brain-computer interface to aid, restore communication
February 19, 2019 - Highly effective solution for detecting onset of aggregation in nanoparticles
February 19, 2019 - Early marker of cardiac damage triggered by cancer treatment identified
February 19, 2019 - Antidepressant drug could save people from deadly sepsis, research suggests
February 19, 2019 - CRISPR technology creates pluripotent stem cells that are ‘invisible’ to the immune system
February 19, 2019 - New study establishes how stress favors breast cancer growth and spread
February 19, 2019 - Midlife Systemic Inflammation Linked to Later Cognitive Decline
February 19, 2019 - Therapy derived from parasitic worms downregulates proinflammatory pathways
February 19, 2019 - Antimicrobial reusable coffee cups are less likely to become contaminated with bacteria, study shows
February 19, 2019 - Harnessing the evolutionary games played by cancer cells to advance therapies
CDK2 protein plays key role in heart damage caused by doxorubicin, finds study

CDK2 protein plays key role in heart damage caused by doxorubicin, finds study

image_pdfDownload PDFimage_print

A new study by Washington State University researchers suggests that a protein called CDK2 plays a critical role in heart damage caused by doxorubicin, a commonly used chemotherapy drug.

Using a rodent model, the researchers showed that doxorubicin increases CDK2 activity in cardiac muscle cells, resulting in cell death. What’s more, they demonstrated that suppressing CDK2 levels alleviated damage to cardiac muscle cells following treatment with doxorubicin.

Published in the Journal of Biological Chemistry, their finding could be used as the basis for future development of treatment strategies and drugs to reduce heart disease risk in cancer survivors, especially those treated in childhood.

Heart disease after cancer treatment

Recent improvements in the diagnosis and treatment of cancer have increased the survival odds of cancer patients. In the U.S., an estimated 16 million people — or 5 percent of the population — are cancer survivors. After cancer recurrence, heart disease is the number one cause of death in this group. Heart toxicity associated with the use of doxorubicin and related chemotherapy drugs is thought to be responsible for cancer survivors’ increased risk of developing heart disease.

“Doxorubicin is very effective at controlling tumor growth, but when used in large cumulative doses it causes damage to cardiac muscle cells that may, over time, lead to heart disease,” said study author Zhaokang Cheng, assistant professor in the WSU College of Pharmacy and Pharmaceutical Sciences.

To better understand how this works at the molecular level, Cheng and his research team looked at cyclin-dependent kinase 2 (CDK2), a protein that is part of a family of more than 20 CDKs that have been implicated in cancer growth.

CDKs are essential proteins in the multiplication and division of different cell types, especially during development. As tumors grow, cancer cells show increased levels of CDK activity, whereas cardiac muscle cells — which do not regenerate in adults — show low levels of CDK.

CDK levels in cancer vs. heart muscle cells

As part of their study, the research team exposed a group of mice to doxorubicin and observed its effects on cardiac muscle cells and levels of CDK2 in those cells, as compared to control mice. Mice that received doxorubicin showed increased cardiac muscle cell death and elevated CDK2 activity in cardiac muscle cells, which came as a surprise.

“It has been known that chemotherapy decreases CDK activity in cancer cells and that this is involved in stopping tumor growth,” Cheng said. “Interestingly, though, when we looked at CDK levels in the heart, chemotherapy increased CDK activity, which was the opposite of what scientists were thinking.”

In other words, while doxorubicin causes cancer cells to stop growing, it appears to make cardiac muscle cells start growing. Since doxorubicin kills cancer cells by causing DNA damage, Cheng suggests that damaged DNA in multiplying cardiac muscle cells eventually causes those cells to stop replicating and die, weakening the heart. He said that could also explain why children — whose hearts are still growing — are more sensitive to heart toxicity from chemotherapy treatment.

CDK inhibitor to reduce heart toxicity

Next, the researchers looked to see whether inhibiting CDK2 could stop heart cell growth and protect the heart from doxorubicin-induced damage. They treated a group of mice with both doxorubicin and roscovitine — an immunosuppressive substance that selectively inhibits CDK2 — and found that heart function in those mice was preserved. The same findings were also confirmed in rat heart cells.

The study shows early promise that CDK inhibitor drugs could be used to stave off heart toxicity in patients being treated with doxorubicin.

CDK inhibitors are a newer class of anticancer drugs. Only three such drugs — palbociclib, ribociclib and abemaciclib — are currently FDA-approved for the treatment of different types of breast cancers, while another dozen or so are being tested in clinical trials.

“Our findings suggest that combining doxorubicin with a CDK inhibitor could be a viable strategy for protecting patients’ hearts while they are being treated for cancer,” Cheng said. “It could provide a much stronger anticancer effect with less toxicity to the heart.”

Tagged with:

About author

Related Articles