Breaking News
March 18, 2018 - Jobs That Keep the Mind Sharp … Even Into Retirement
March 18, 2018 - Facial Scarring Improved with Botulinum Toxin
March 18, 2018 - Data detectives shift suspicions in Alzheimer’s to inside villain
March 18, 2018 - Shorter Preventive TB Tx Effective for HIV+ Patients
March 18, 2018 - New technique for identifying alcoholism puts treatment options at patients’ and providers’ fingertips
March 18, 2018 - Researchers uncover four microRNAs as potential biomarkers for atrial fibrillation
March 18, 2018 - IRX Therapeutics Announces Initiation of Phase 2 Clinical Trial of IRX-2 in Squamous Cervical or Vulvar Intraepithelial Neoplasia 3
March 18, 2018 - OncoBreak: Learning from Silence; ‘Rigged’ Drug System; NCCN Guidelines Questioned
March 18, 2018 - The coffee cannabis connection
March 18, 2018 - Novel centrifugal-flow pump for heart failure patients provides improved long-term outcomes
March 18, 2018 - U.S. FDA Accepts New Drug Application for Prucalopride (SHP555) for Chronic Idiopathic Constipation
March 18, 2018 - Cath Lab Recap: iFR vs FFR $$; Ridaforolimus-Eluting Stent
March 18, 2018 - Tree care workers need better training to handle dangers on the job, study finds
March 18, 2018 - Dementia patients do not undergo diagnostic evaluation at onset of disease, study finds
March 18, 2018 - Transplanting enhanced interneurons restores brain rhythms in mouse model of Alzheimer’s
March 18, 2018 - Gene Therapy Flops for Critical Limb Ischemia
March 17, 2018 - Study spotlights risks in anesthesiologist handoffs
March 17, 2018 - Verb fluency test may be useful tool for differential diagnosis of cognitive failure
March 17, 2018 - Health Tip: Suggestions to Improve Your Cholesterol
March 17, 2018 - Fructans Suspect in Non-Celiac Gluten Sensitivity
March 17, 2018 - Aspirin therapy appears safe before thyroid surgery
March 17, 2018 - Minimally invasive surgical device may one day provide lasting heart repair
March 17, 2018 - UIH and RaySearch enter into new partnership
March 17, 2018 - Is BMI Too Inexact? | Medpage Today
March 17, 2018 - Sleep apnea study finds male-female differences in cerebral cortex thickness, symptoms
March 17, 2018 - Leicester research could help identify people with asthma of different severities
March 17, 2018 - Biosense Webster enrolls and treats first AF patient in clinical study of new RF balloon catheter
March 17, 2018 - Participants in rogue herpes vaccine research take legal action
March 17, 2018 - Imara Doses First Patient in Phase 2a Clinical Trial of IMR-687 for Sickle Cell Disease
March 17, 2018 - AAP: Prevent Medication Errors by Improving Processes
March 17, 2018 - Severe sleep apnea during REM sleep tied to acute CV events
March 17, 2018 - Alzheimer’s disease also affects small blood vessels
March 17, 2018 - Jazz Pharmaceuticals Announces FDA Acceptance of NDA for Solriamfetol (JZP-110) for Excessive Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea
March 17, 2018 - Switching Biologics in Psoriasis Care
March 17, 2018 - Polygenic risk score may identify alzheimer’s risk in younger populations
March 17, 2018 - Genetic heart mutations account for fewer sudden and unexplained infant deaths
March 17, 2018 - Clinical trial to test efficacy of stem cell transplants in stopping ALS muscle deterioration
March 17, 2018 - Researchers team up to improve life for children with microcephaly
March 17, 2018 - Health guide for young women regarding labiaplasty
March 17, 2018 - Inhaled Nitrite Flops as HFpEF Therapy
March 17, 2018 - California mental health tax providing services to needy in L.A. County, study finds
March 17, 2018 - Cancer survivors become fatigued more quickly than their peers, study finds
March 17, 2018 - Study finds common presence of nightmares among U.S. military personnel
March 17, 2018 - Yellow fever outbreak in Brazil necessitates vaccination for travelers
March 17, 2018 - Health Tip: Waist Size May Help Predict Heart Attack
March 17, 2018 - Low-Dose Combo Pill Successfully Takes Down High BP
March 17, 2018 - Most children with sickle cell anemia not receiving key medication to stay healthy
March 17, 2018 - YCC launches new Yale Center for Immuno-Oncology
March 17, 2018 - My Job Isn’t to Move Patients Quickly
March 17, 2018 - Achoo! Cold, Flu, or Something Else?
March 17, 2018 - For girls who mature early, psychological problems last into adulthood
March 17, 2018 - Researchers find new method to restore movement sensation in patients with prosthetic arms
March 17, 2018 - Older patients with colorectal cancer at increased risk of cardiovascular morbidity
March 17, 2018 - Chemical peels can be safe treatment option for people with darker skin
March 17, 2018 - Rutgers University study highlights the need for improved safety in tree-care operations
March 17, 2018 - Review reveals essential themes for successful care transitions for persons with dementia
March 17, 2018 - Subset of immune cells critical for ensuring healthy weight gain, study shows
March 17, 2018 - Genetic variant discovery could improve safety, effectiveness of drugs for asthma and COPD
March 17, 2018 - New 3D tissue model of developing heart could be used to test safety of drugs during pregnancy
March 17, 2018 - Study on infant bone strength could aid in design of safer car seats
March 17, 2018 - Online program increases depression treatment rates among adolescent mothers
March 17, 2018 - Pulmatrix Announces First Subject Dosed in Phase 1 Clinical Trial of Pulmazole – an Inhaled Dry-Powder iSPERSE™ Formulation of Itraconazole
March 17, 2018 - Diet During Pregnancy May Cut Offspring Allergy Risk
March 17, 2018 - Faulty cellular membrane ‘mix’ linked to Parkinson’s disease
March 17, 2018 - For aspiring doctors with disabilities, many medical schools come up short
March 17, 2018 - Common genetic variation shown to increase Alzheimer’s risk
March 17, 2018 - Switching to glo vapor reverses biological effects caused by smoke exposure
March 16, 2018 - Climate change spurs proliferation of disease-bearing insects, increases exposure to viral infections
March 16, 2018 - FDA Accepts Remoxy NDA For Review
March 16, 2018 - Docs to the Rescue? | Medpage Today
March 16, 2018 - Shedding a tear may help diagnose Parkinson’s disease
March 16, 2018 - Study elucidates underlying cause of brain injury in stroke
March 16, 2018 - Neuroscientists identify role of primary visual cortex in integrating head and visual movement signals
March 16, 2018 - MIT engineers develop new technology that could improve drug evaluation
March 16, 2018 - IBN’s green tea-based drug nanocarriers show superior tumor-killing performance
March 16, 2018 - NIH researchers explore genetic clocks to understand role of aging in neurodegeneration
March 16, 2018 - FDA Alert: Alka-Seltzer Plus Products: Recall
March 16, 2018 - DOJ Repeats Threat to Hold Opioid Prescribers Accountable
March 16, 2018 - PFASs, chemicals commonly found in environment, may interfere with body weight regulation
March 16, 2018 - Study reveals reduced risk of dementia for physically fit women
Study finds combination therapy as effective strategy to treat ovarian cancers

Study finds combination therapy as effective strategy to treat ovarian cancers

image_pdfDownload PDFimage_print

Researchers at The Wistar Institute have found that combining PARP inhibitors, recently approved for the treatment of BRCA-mutant ovarian cancer, with another small molecule inhibitor was effective to treat ovarian cancers without BRCA1 and BRCA2 gene mutations. This study was published online in Cell Reports.

Ovarian cancer is the most lethal gynecological malignancy and therapeutic options remain limited. Mutations in the BRCA1 and BRCA2 genes, which function in the repair of DNA damage and in maintaining the stability of the genetic material, are common and have a causative role in the development of this type of cancer. Cells with a defect in these genes have non-functional BRCA proteins and cannot properly repair DNA damage. As a result, they are more likely to develop further genetic alterations that can lead to cancer.

“By blocking another member of the DNA repair pathway, PARP inhibitors are an effective strategy to kill BRCA-mutant cancer cells and have recently been approved for the treatment of ovarian cancer, but how to expand their utilities into BRCA-proficient cancers remained to be explored,” said Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, professor and co-program leader of the Gene Expression and Regulation Program. “We identified an effective strategy to sensitize BRCA-proficient ovarian cancers to PARP inhibitors and extend their clinical efficacy to a larger group of patients.”

Previous research has shown that, in the absence of BRCA mutations, simultaneous inhibition of other DNA repair proteins, such as WEE and TOPBP1, can sensitize cancer cells to PARP inhibitors. Zhang and colleagues found that blocking the activity of the BRD4 transcriptional regulator with a small molecule inhibitor resulted in reduced expression of DNA repair proteins, including WEE and TOPBP1. Importantly, this resulted in enhanced sensitivity of BRCA-proficient ovarian cancer cells to a PARP inhibitor, as the combination of both inhibitors was able to induce cell death.

Mechanistically, inhibition of BRD4, which belongs to the BET family of proteins, allowed cells with DNA damage caused by the PARP inhibitor to proceed into cell division without repairing the damage, thus resulting in cell death by a phenomenon called mitotic catastrophe.

The team tested the combination of PARP and BET inhibitors in vivo in a mouse model of ovarian cancer with normal BRCA1 and BRCA2. While neither of the two inhibitors alone had an effect on tumor growth, the combination of the two resulted in significant reduction of tumor burden without any overt toxicity.

“The combined use of these inhibitors can be potentially applied to a broad spectrum of malignancies regardless of the BRCA genes mutational status,” said Sergey Karakashev, Ph.D., co-first author of the study and a postdoctoral researcher in the Zhang Lab. “Therefore, we anticipate that our work will have far-reaching applications in the development of novel combinatory cancer therapeutics.”

Tagged with:

About author

Related Articles