Breaking News
August 17, 2018 - Peer Comparisons Can Decrease Risky Prescribing Patterns
August 17, 2018 - Susceptible genes identified for childhood chronic kidney disease
August 17, 2018 - Bacterial armor could be new target for antibiotics | News Center
August 17, 2018 - FDA expands approval of Vertex’ cystic fibrosis medicine to treat children aged 12 to
August 17, 2018 - Give Your Child a Head Start With Math
August 17, 2018 - Ground-breaking study tests whether rejected livers can be made viable for transplantation
August 16, 2018 - New algorithm could improve diagnosis of rare diseases | News Center
August 16, 2018 - SCHILLER introduces latest generation of ECG device, CARDIOVIT AT-102 G2
August 16, 2018 - Proper treatment, refraining from smoking can reduce heart disease risk from type 2 diabetes
August 16, 2018 - Mount Sinai study could transform treatment for patients with retinal degenerative diseases
August 16, 2018 - Penn researchers develop first mouse model of idiopathic pulmonary fibrosis
August 16, 2018 - Four tips to help prevent fall allergy symptoms
August 16, 2018 - Women’s Preventive Services Initiative says screen all women annually for urinary incontinence
August 16, 2018 - At Stanford, patient discovers the source of her headaches, nausea | News Center
August 16, 2018 - To Prevent Injuries in Young Baseball Players, Chris Ahmad Reaches Out to Parents
August 16, 2018 - Restoring blood flow may be linked to longer survival in patients with critical limb ischemia
August 16, 2018 - New model of genetically engineered immune cells may help fight solid tumors
August 16, 2018 - Maternal stress increases anxious and depressive-like behaviors in female offspring
August 16, 2018 - Childhood exposure to secondhand smoke increases risk of COPD death in adulthood
August 16, 2018 - Scientists uncover key control mechanism of DNA replication
August 16, 2018 - NIH begins first-in-human trial of experimental live, attenuated Zika virus vaccine
August 16, 2018 - Two diabetes medications don’t slow progression of type 2 diabetes in youth
August 16, 2018 - 5 Questions: How Stanford research is making MRI scans safer for kids | News Center
August 16, 2018 - Columbia Celebrates 25th Anniversary of White Coat Ceremony
August 16, 2018 - Phonak’s new smallest and most discreet Virto B-Titanium hearing aid
August 16, 2018 - New project aims to study growth of water-based microorganisms
August 16, 2018 - Immune cell found to play important role in photosensitivity
August 16, 2018 - Higher social dominance linked to faster decision-making in men
August 16, 2018 - Blood test in early pregnancy could determine a woman’s later risk for gestational diabetes
August 16, 2018 - New research confirms link between DDT exposure and autism
August 16, 2018 - Neurodevelopmental Anomalies, Birth Defects Linked to Zika ID’d
August 16, 2018 - Risk of heart failure up in ALVSD patients with diabetes
August 16, 2018 - Exercise reduces symptoms and fatigue in patients with chronic kidney disease
August 16, 2018 - Study reveals role of RUNX proteins in DNA repair
August 16, 2018 - New research finds no harm from average salt consumption
August 16, 2018 - Researchers develop new way of testing bacterial resistance to antibiotics
August 16, 2018 - Magnetic gene in aquarium fish could open doors to treatment for epilepsy, Parkinson’s
August 16, 2018 - Five tips for successful long-term breastfeeding
August 16, 2018 - Researchers identify brain networks involved in object naming
August 16, 2018 - Promoting HPV Vaccine Doesn’t Prompt Risky Sex by Teens: Study
August 16, 2018 - Treating Rheumatoid Arthritis: Search for a Cure
August 16, 2018 - Research shows in the long run, charcoal toothpaste likely won’t whiten teeth
August 16, 2018 - Seattle Children’s opens new clinic to provide convenient access to pediatric specialty care services
August 16, 2018 - Curious case of the lost contact lens
August 16, 2018 - GN Hearing unveils world’s first Premium-Plus hearing aid
August 16, 2018 - Parental life span linked with increased longevity and health in daughters
August 16, 2018 - Health leaders reveal ten most important medicines in NHS history
August 16, 2018 - Mobile health devices diagnose hidden heart condition in at-risk populations
August 16, 2018 - When it comes to shedding pounds, it pays to think big
August 16, 2018 - Liva Healthcare announces appointment of Thomas Cooke as clinical services manager in the UK
August 16, 2018 - New digital pharmacy aims to help people living with chronic care conditions
August 16, 2018 - Preventing ACL injuries in high school athletes
August 16, 2018 - Experts provide insight into novel concepts and approaches for stroke rehabilitation
August 16, 2018 - Scientists reverse congenital blindness in mouse model
August 16, 2018 - Study shows link between use of benzodiazepines and increased risk of Alzheimer’s disease
August 16, 2018 - Study provides new insight into how ‘trash bag of the cell’ traps and seals off waste
August 16, 2018 - Trial shows PARP inhibitor as novel treatment option for patients with advanced breast cancers
August 16, 2018 - Prenatal exposure to violence increases toddlers’ aggressive behavior to their mothers
August 16, 2018 - Can manipulating gut microbes improve cardiac function in patients with heart failure?
August 16, 2018 - Hearts of newborn piglets can completely heal after heart attacks
August 16, 2018 - Ablating the mutant p53 gene in mice with colorectal cancer inhibits tumor growth
August 16, 2018 - Higher BMI in people with prediabetes related to evening preference and lack of sufficient sleep
August 16, 2018 - Using peripheral nerve blocks to treat facial pain may produce long-term pain relief
August 16, 2018 - Neural stem cells are the key to tail regeneration
August 16, 2018 - Study compares genetic and neural contributions to ADHD in children with or without TBI
August 16, 2018 - Adding energy drinks to alcohol may exacerbate negative effects of binge drinking
August 16, 2018 - Eye Examination Can Help Detect Abuse in Children
August 16, 2018 - Know the Difference: Rheumatoid Arthritis or Osteoarthritis?
August 16, 2018 - From ‘sea of mutations,’ two possible cancer links rise to the surface
August 16, 2018 - Does medical school take too long?
August 16, 2018 - Brown University researchers reveal key physical properties of ‘giant’ cancer cells
August 16, 2018 - Regular resistance training improves exercise motivation
August 16, 2018 - Feds urge states to encourage cheaper plans off the exchanges
August 16, 2018 - Seven activities that prevent you from getting quality sleep during summer
August 16, 2018 - Five ways to tell if your baby is getting enough milk from breastfeeding
August 16, 2018 - From Pigs to Peacocks, What’s Up With Those ‘Emotional-Support Animals’?
August 16, 2018 - Breast cancers enlist the help of normal cells to help them spread and survive
August 16, 2018 - Engaging with “high-need” patients outside the clinic
August 16, 2018 - Research illuminates how online forum may offer suicide prevention support for males
August 16, 2018 - Researchers identify way to grow immune cells at large scale for preventing cancer reoccurrence
Study may explain how chemoresistance evolves over time in some triple-negative breast cancers

Study may explain how chemoresistance evolves over time in some triple-negative breast cancers

image_pdfDownload PDFimage_print

Triple-negative breast cancer (TNBC) is an aggressive form of the disease accounting for 12 to 18 percent of breast cancers. It is a scary diagnosis, and even though chemotherapy can be effective as standard-of-care, many patients become resistant to treatment. A team at The University of Texas MD Anderson led a study which may explain how resistance evolves over time, and potentially which patients could benefit from chemotherapy.

Results from a study led by Nicholas Navin, Ph.D., associate professor of Genetics, were published today in the April 19, 2018 online issue of Cell. Their findings indicate breast cancer cell resistance to chemotherapy may be pre-existing and the cells may even adapt to become resistant when confronted by the chemotherapy itself.

To answer how a cell becomes resistant to chemotherapy, one must understand that cancer often begins with a clone – a single mutated cell that either can be destroyed by the immune system, or mutated further as subclones, genetic aberrations resulting in an ever-evolving cellular pathway to cancer.

“An unresolved question is whether resistance is caused by the selection of rare pre-existing clones or, alternatively, through the acquisition of new genomic aberrations,” said Navin. “Our data showed that resistant genotypes, or genes prone to being cancer-resistant, were pre-existing and adaptively selected by the initial treatment known as neo-adjuvant chemotherapy, but also requires further changes in gene expression programs to become fully resistant.”

Neo-adjuvant chemotherapy (NAC) is the standard of care for many TNBC patients, who lack estrogen and progesterone receptors as well as human epidermal growth factor 2 (HER2) receptor, making them ineligible for hormone or anti-HER2 therapy. While NAC is effective in some TNBC patients, approximately half will develop chemotherapy resistance, leading to poor overall survival.

“A major gap in knowledge is whether chemoresistance arises due to the selection and expansion of pre-existing subclones called adaptive resistance or through new mutations resulting from the chemotherapy, a phenomenon known as acquired resistance,” said Navin. “Previous genomic studies in other cancers have shown either adaptive or acquired resistance in different cancer types.”

Navin’s group studied 20 TNBC patients treated with NAC. They looked at genetic changes by deeply sequencing the coding regions of genes across the genome. They sought to understand whether new genetic mutations occurring after chemotherapy erupted spontaneously due to acquired resistance, or whether the mutations already existed at very low levels prior to treatment.

“What we found were two distinct classes of clonal dynamics – extinction and persistence,” said Navin. “In the clonal extinction patients, NAC eliminated the tumor cells, leaving only normal cell types post-treatment. Clonal persistent patients harbored a larger number of residual tumor cells with genotypes and phenotypes that were altered in response to NAC.”

Using single-cell DNA and RNA sequencing, his team performed a detailed analysis of eight clonal persistent patients, measuring miniscule portions of DNA and RNA and found responses to NAC were pre-existing, thus adaptively selected. However, the expression of resistant genes was acquired by subsequent reprogramming as a result of chemotherapy.

“Our data support a model of chemoresistance in which two modes of evolution, adaptive and acquired, were operating to establish chemo-resistant tumor mass,” said Navin. “This data has important clinical implications.”

Navin’s group believes pre-existence of chemoresistant genotypes in tumors indicates there may be diagnostic opportunities for detecting chemoresistant clones in TNBC patients prior to receiving NAC. Their findings that TNBC patients fall into clonal extinction or clonal persistent groups may be applicable to patient outcomes or survival.

“Lastly, our data raise the possibility of therapeutic strategies to overcome chemoresistance by targeting pathways identified in this study,” said Navin. “Future work will need to be performed in a larger group of TNBC patients to fully understand this evolutionary model and gene-related chemoresistance.”

Source:

https://www.mdanderson.org/newsroom/2018/04/study-may-explain-why-some-triple-negative-breast-cancers-are-resistant-to-chemotherapy.html

About author

Related Articles