Breaking News
February 21, 2018 - Scientists uncover how newly discovered gene helps grow blood vessels
February 21, 2018 - Brain’s quality control process holds clues to obesity’s roots
February 21, 2018 - Researchers to study whether menstrual cups can help prevent vaginal infections
February 21, 2018 - MS patients who feel stigmatized more likely to suffer from depression
February 21, 2018 - Vitamin D supplementation during pregnancy could protect against childhood obesity
February 21, 2018 - Lower-Quality Medical Tx Might Have Skewed Key PCI vs CABG Trials
February 21, 2018 - Love and fear are visible across the brain instead of being restricted to any brain region
February 21, 2018 - Adults with congenital heart disease have increased risk for dementia, study finds
February 21, 2018 - Clinical trial studying type 1 diabetes reaches full enrollment
February 21, 2018 - Father’s stress affects the brain development of offspring, mice study shows
February 21, 2018 - ESRD Death Declines in Vasculitis Patients
February 21, 2018 - Taking ibuprofen for long periods found to alter human testicular physiology
February 21, 2018 - Google AI device could predict a person’s risk of a heart attack
February 20, 2018 - FDA Approves Domestic Source for Tc-99m Isotopes
February 20, 2018 - Sanofi rejects refund demand faces Philippine suit over dengue vaccine (Update)
February 20, 2018 - Researchers discover that activation of specific enzyme may help suppress tumor metastasis
February 20, 2018 - Blood or marrow transplantation survivors have higher risk of cognitive impairment
February 20, 2018 - Booze Beats Pot at Being Unhealthy: Oregon Poll
February 20, 2018 - Morning Break: ’20 Years Late’; Drugs in the Dirt; Catching Flu in the Dorm
February 20, 2018 - Another piece to the puzzle in naked mole rats’ long, cancer-free life
February 20, 2018 - Scientists identify four viruses that can produce insulin-like hormones
February 20, 2018 - New e-Health solution developed to prevent cardiovascular disease, dementia in senior citizens
February 20, 2018 - New genetic risk score could help guide screening decisions for prostate cancer
February 20, 2018 - Study finds higher risk of stroke among blacks with atrial fibrillation than whites
February 20, 2018 - Physical activity could be used as strategy for diabetes prevention
February 20, 2018 - Researchers develop sensing method for early detection of cancer and diabetes
February 20, 2018 - New wearable electronics could be game-changer for stroke rehabilitation
February 20, 2018 - Immune history influences person’s response to flu vaccine
February 20, 2018 - Research findings could help develop new drugs to prevent, treat dry eye disease
February 20, 2018 - Serenity Now! Learn to Have Patience with Patients
February 20, 2018 - Computer simulation addresses the problem of blood clotting
February 20, 2018 - Women with type 1 diabetes not protected against coronary artery disease
February 20, 2018 - Persistent bloating can be a sign of ovarian cancer, warns charity
February 20, 2018 - Trump administration proposes rule to loosen curbs on short-term health plans
February 20, 2018 - Key protein involved in epigenetic regulation of gene expression guides skin cell renewal
February 20, 2018 - Heart attack symptoms often missed in women
February 20, 2018 - Diagnosis of celiac disease takes 3.5 years for patients who do not report GI symptoms
February 20, 2018 - Study reveals functional dynamics of ion channels
February 20, 2018 - Study explores link between mortality risk and combustible tobacco use
February 20, 2018 - ‘She Trusted Me, and I’d Turned Her Away’
February 20, 2018 - AbbVie and Voyager Therapeutics collaborate to develop new treatments for tauopathies
February 20, 2018 - Fast food makes the immune system more aggressive in the long term
February 20, 2018 - Therapeutic target for glaucoma could have treatment ramifications for Alzheimer’s and Parkinson’s
February 20, 2018 - Overcoming Negative Reviews | Medpage Today
February 20, 2018 - MyD88—villain of allergies and asthma
February 20, 2018 - Food scientists develop rapid screening technique to detect pesticide residue in vegetables
February 20, 2018 - Lab-grown cerebellar cells may help explain how ASD develops at molecular level
February 20, 2018 - Scientists explore connection between bad sleep habits and stiff blood vessels
February 20, 2018 - New Treatment Apalutamide (Erleada) Approved for Prostate Cancer That Resists Hormone Therapy
February 20, 2018 - Do You Really Need My Signature on That?
February 20, 2018 - HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection
February 20, 2018 - Diabetes does not increase work-loss years due to early retirement
February 20, 2018 - Researchers aim to find out how PTSD affects decisions of police
February 20, 2018 - UH Cleveland Medical Center explores novel treatments for uterine fibroids
February 20, 2018 - Flu Vax Efficacy 25% Against Predominant H3N2 Strain So Far
February 20, 2018 - HIV screening most optimal at 25 years of age if no risk factors
February 20, 2018 - Loyola Medicine primary care physician offers advice to minimize risk of flu
February 20, 2018 - Safe sleep recommendations for parents that may help reduce child’s risk of SUID
February 20, 2018 - Why Do So Few Docs Have Buprenorphine Waivers?
February 20, 2018 - Low levels of alcohol good for the brain
February 20, 2018 - Experimental treatment improves invisible symptoms of a man with spinal cord injury
February 20, 2018 - Myriad’s EndoPredict offers better prediction of breast cancer recurrence, analysis shows
February 20, 2018 - Researchers identify fifteen genes that determine our facial features
February 20, 2018 - Morning Break: New Health IT Player; Luxturna No Bargain; Nuclear Freakout
February 20, 2018 - How does it compare? Hospice care at home, at assisted living facility, at nursing home
February 19, 2018 - Scientists develop water-soluble warped nanographene for bioimaging
February 19, 2018 - It’s Not Your Imagination: You’re Hungrier After Losing Weight
February 19, 2018 - Antihypertensive Use At Delivery Rising in Preeclampsia
February 19, 2018 - A centuries-old math equation used to solve a modern-day genetics challenge
February 19, 2018 - Liquid biopsies could be used as new predictive marker for metastatic TNBC
February 19, 2018 - Russian researchers develop new multi-layered biodegradable scaffolds
February 19, 2018 - Are ‘Vaccine Skeptics’ Responsible for Flu Deaths?
February 19, 2018 - Hidden genetic effects behind immune diseases may be missed, study suggests
February 19, 2018 - Emergency nurses experience regular verbal and physical abuse
February 19, 2018 - Study sheds light on biology that guides behavior across different stages of life
February 19, 2018 - Morning Break: Transgender Breast Feeding; Brazilian ‘Pro-Vaxxers’; Post-Stroke Exercise
February 19, 2018 - Meningitis vaccination strategy in Africa found to be effective, economical
February 19, 2018 - Researchers uncover how excess calcium may influence development of Parkinson’s disease
February 19, 2018 - Psoriasis drug also effective at reducing aortic inflammation
February 19, 2018 - Excess emissions can make serious contributions to air pollution, study shows
Study uncovers key mechanism by which tumors develop resistance to radiation therapy

Study uncovers key mechanism by which tumors develop resistance to radiation therapy

image_pdfDownload PDFimage_print

A Ludwig Cancer Research study has uncovered a key mechanism by which tumors develop resistance to radiation therapy and shown how such resistance might be overcome with drugs that are currently under development. The discovery addresses a longstanding challenge: as many as 40% of large tumors develop resistance to radiotherapy, significantly complicating treatment. Overcoming such resistance could go a long way toward treating tumors, especially those that cause significant discomfort to patients and resist other modes of therapy or cannot be surgically removed.

“It has been known for some time that radiation induces inflammation, and we’ve shown in our earlier work that it does so through a molecular sensor found in cells known as the stimulator of interferon genes, or STING,” says Ralph Weichselbaum, co-director of the Ludwig Center at Chicago, who led the study with Yang-Xin Fu of the UT Southwestern Medical Center. “However, there’s a dark side to radiation: after it causes good inflammation–which mounts an immune attack on cancer cells in the irradiated tumor–it causes a bad kind of inflammation that suppresses immune responses.”

STING detects DNA fragments inside cells, fragments generated by the damage high energy radiation does to chromosomes. In previous studies, Weichselbaum, Fu and their colleagues showed that STING links the detection of such fragments to the production of immune factors known as type 1 interferons. These factors ultimately boost the activation of killer T cells–immune cells that attack sick and cancerous cells–and cause much of the destruction of tumors associated with radiation therapy.

The researchers hypothesized that this same STING/Type 1 interferon signaling cascade might also account for the resistance tumors develop to extended radiotherapy. They report in the current issue of Nature Communications that this indeed appears to be the case. The immunosuppression, they found, is caused by an influx of particular suppressive immune cells known as monocytic myeloid-derived suppressor cells (M-MDSCs) that are drawn into the tumor due to long-term STING/Type 1 interferon signaling.

Using mouse models of lung and colon tumors, the researchers found that the tumor-infiltrating M-MDSCs express a cell surface receptor known as CCR2, whose ligand–or binding target–is expressed by cells upon STING activation. They then showed that resistance to radiotherapy was significantly reduced in mice engineered to lack CCR2.

To determine whether the effect might be translated into clinical practice, the researchers checked whether it could be reproduced in mice that express CCR2 with the use of antibodies to the receptor. They found it could. Most notably, in both types of mice the destruction of tumors was significantly boosted when the radiation therapy was delivered along with a STING-activating drug and anti-CCR2 antibodies.

“What we did by combining those treatments was to stimulate the immune system while alleviating immune suppression, and that worked best to improve responses to radiotherapy–more than either did alone,” says Weichselbaum.

Pharmaceutical companies are developing STING activating drugs for cancer therapy, and one is currently being evaluated in clinical trials in combination with checkpoint blockade–a type of immunotherapy that boosts T cell attack on certain types of tumors. Similarly, antibodies to CCR2 are also being developed as potential immunotherapeutic agents. The current study lays the groundwork for combining these experimental drugs to improve the effects of radiotherapy for a variety of solid tumors.

“What we’ve shown in this preclinical study is that if you block the influx of these MDSCs, you can, to a large extent, preempt resistance to radiation therapy,” says Weichselbaum. “Our current study is of immediate relevance to radiation therapy, but we think it may also have significant implications for chemotherapy and immunotherapy as well.”

Source:

http://www.ludwigcancerresearch.org/

Tagged with:

About author

Related Articles