Breaking News
September 19, 2018 - Janssen Submits New Drug Application to U.S. FDA Seeking Approval of Erdafitinib for the Treatment of Metastatic Urothelial Cancer
September 19, 2018 - Suicide: A public health crisis
September 19, 2018 - Stanford team will participate in NIH-funded study of tobacco policies | News Center
September 19, 2018 - Women with high levels of anti-Müllerian hormone more likely to develop breast cancer
September 19, 2018 - Effects of prematurity found to be more severe for the brains of males than females
September 19, 2018 - NIH funds CWRU to investigate new imaging approach for diagnosing peripheral arterial disease
September 19, 2018 - NUS researchers develop new device for quick and accurate screening of diseases
September 19, 2018 - Leading nutritionist explains about different types of iron in oral supplements
September 19, 2018 - New Crest Gum & Enamel Repair toothpaste may boost enamel repair and reverse gingivitis
September 19, 2018 - Analysis does not find any safety concerns of bivalent HPV vaccine
September 19, 2018 - Many Older Adults Transition to Long-Term Benzodiazepine Use
September 19, 2018 - Caregiving – resources – older adults: MedlinePlus Medical Encyclopedia
September 19, 2018 - Research shows that cystic fibrosis impacts growth in the womb
September 19, 2018 - Study shows how head, neck positioning affects concussion risk | News Center
September 19, 2018 - Antioxidant in green tea helps sneak therapeutic RNAs into cells
September 19, 2018 - Excess pregnancy weight gain affects cardiometabolic risk in offspring
September 19, 2018 - Penn researchers find common thread linking almost all TNR expansion diseases
September 19, 2018 - Ipsen receives approval from Health Canada for CABOMETYX tablets for treating renal cell carcinoma
September 19, 2018 - Researchers use CRISPR screen to reveal new targets in squamous cell carcinomas
September 19, 2018 - UGR to coordinate the European H2020 project focused on Smart Personalized Nutrition
September 19, 2018 - Mumps Spread Quickly at Texas Cheerleading Meets: Study
September 19, 2018 - Addressing child stunting in Pakistan is critical
September 19, 2018 - Innovative system makes hospitals, clinics accessible for people with visual impairments
September 19, 2018 - CXCL14 protein is secreted by brown adipose tissue and has beneficial effects in metabolic diseases
September 19, 2018 - Air pollution increases risk of dementia
September 19, 2018 - Inequality issues persist even under new U.S. kidney transplant allocation system
September 19, 2018 - New study reveals mechanisms that lead to cognitive decline in Type 2 diabetes
September 19, 2018 - FDA launches new comprehensive effort to educate kids about dangers of e-cigarettes
September 19, 2018 - Study reveals mechanism underlying plants’ ability to signal defense
September 19, 2018 - Researchers harness Zika virus vaccine under development to target glioblastoma
September 19, 2018 - Novel deep learning drug discovery platform gets £1 million innovation boost
September 19, 2018 - Sensor array may detect de novo Parkinson’s disease in breath
September 19, 2018 - A roadmap for the future of electronic health records
September 19, 2018 - Surprising research showing peptide adaptability may pave way to develop immunotherapies
September 19, 2018 - Amyloid β protein makes comeback as therapeutic target for Alzheimer’s disease
September 19, 2018 - Alcon expands its global support of eye care professionals through Alcon Experience Academy
September 19, 2018 - Study gives new insights into how cells leverage GPCRs to control inflammation
September 19, 2018 - Automatic relevance detection in ophthalmic surgery videos
September 19, 2018 - UNIST to accelerate discovery, development of new medicines for incurable diseases
September 19, 2018 - Novel clinical trial to examine cannabis as potential treatment for essential tremor
September 19, 2018 - Salsa dancers have lower injury rates than Spanish, aerobic or Zumba dancers
September 19, 2018 - AmpliPhi receives positive feedback from FDA for its AB-PA01 product targeting P.aeruginosa infections
September 19, 2018 - Bristol-Myers Squibb’s Novel, Oral, Selective TYK2 Inhibitor Delivered Significant Skin Clearance in Patients with Moderate to Severe Plaque Psoriasis in Phase 2 Trial
September 19, 2018 - Can work stress contribute to Parkinson’s disease risk?
September 19, 2018 - Global Climate Action Summit: A focus on kids and climate
September 19, 2018 - Vitamin D may reduce breast cancer mortality in women with lower BMI
September 19, 2018 - Targeted Lung Denervation procedure significantly reduces COPD problems
September 19, 2018 - FDA-approved ‘safe’ daily BPA exposure may contribute to insulin resistance
September 19, 2018 - Research finds physical connection between the brain’s fluid reservoirs and meningeal lymphatics
September 19, 2018 - UCalgary study could help physicians make better treatment decisions for stroke
September 19, 2018 - Biomedical review finds failure rates in some surgical mesh treatments to be unacceptably high
September 19, 2018 - Researchers develop more accurate measure of body fat
September 19, 2018 - Doctors and students rally to support gun violence research, education
September 19, 2018 - LEO Pharma and MorphoSys announce expansion of strategic alliance to develop peptide-derived drugs
September 19, 2018 - Seniors in pain hop aboard the canna-bus
September 19, 2018 - New compound could prevent malaria parasites from maturing inside mosquito
September 19, 2018 - Scientists find alterations in blood flow in response to body position change
September 19, 2018 - UNC Health Care extends free access to virtual care service in the aftermath of Hurricane Florence
September 19, 2018 - Opioid Refills Rare After Rhinoplasty
September 19, 2018 - Corn, obesity, and navigating healthy eating choices as a parent
September 19, 2018 - Journal editor aims to prompt thoughtful review of ethics in precision health
September 19, 2018 - Researchers identify key step in how plant cells respond to pathogens
September 18, 2018 - Researchers analyze how exposure to silver nanoparticles affects zebrafish
September 18, 2018 - Study shows air pollution may be bad for the fetus
September 18, 2018 - Coffee May Have Another Perk for Kidney Patients
September 18, 2018 - Tongue-in-cheek Nobels honor nutritional analysis of cannibalism, roller-coaster kidney stones treatment
September 18, 2018 - Progress, priorities, challenges are focus of State of Stanford Medicine | News Center
September 18, 2018 - Established Alzheimer’s Risk Gene Has a New Role
September 18, 2018 - Hospitalization after antibiotic initiation found to be higher for people with Alzheimer’s disease
September 18, 2018 - Many children with special healthcare needs do not have access to ‘PCMH-concordant’ care
September 18, 2018 - Investigational nasal influenza vaccine tested in children and teens
September 18, 2018 - Lymphatic vessels surrounding the brain play crucial role in multiple sclerosis, research suggests
September 18, 2018 - New fiber laser-based ultrasound sensor may have potential applications in medical diagnostics
September 18, 2018 - Protect your heart and health during ‘dog days’ of summer
September 18, 2018 - Faculty receive awards for promise in biomedical research, clinical care | News Center
September 18, 2018 - Digital games for CVD-related self-management improve exercise capacity and energy expenditure
September 18, 2018 - Aluminum inclusions help enhance adsorption of chemo drugs onto active carbon delivery capsule
September 18, 2018 - Adding PET scans to CT imaging can change treatment for women with cervical cancer
September 18, 2018 - UCSF awarded $20 million grant to study impacts of new, emerging tobacco products
September 18, 2018 - Human brains may be wired to prefer lying on the couch, suggests research
Study provides clues to how cancer cells develop resistance to chemotherapies

Study provides clues to how cancer cells develop resistance to chemotherapies

image_pdfDownload PDFimage_print

About half of all drugs, ranging from morphine to penicillin, come from compounds that are from-;or have been derived from-;nature. This includes many cancer drugs, which are toxic enough to kill cancer cells.

So how do the organisms that make these toxic substances protect themselves from the harmful effects? Scientists on the Florida campus of Scripps Research have uncovered a previously unknown mechanism-;proteins that cells use to bind to a toxic substance and sequester it from the rest of the organism.

“Thanks to this discovery, we now know something about the mechanisms of resistance that’s never been known before for the enediyne antitumor antibiotics,” says study senior author Ben Shen, PhD, professor and co-chair of the Scripps Research Department of Chemistry.

The work has important implications for understanding how human cancer cells develop resistance to natural product-based chemotherapies. Furthermore, the microbiome may play a role in drug resistance. The study was published today in the journal Cell Chemical Biology.

“This mechanism could be clinically relevant for patients getting these drugs, so it’s very important to study it further,” says Shen.

Natural products-;chemical compounds produced by living organisms-;are considered one of the best sources of new drugs and drug leads. “They possess enormous structural and chemical diversity compared with molecules that are made in the lab,” Shen says. Natural products may come from flowers, trees or marine organisms such as sponges. One of the most common sources, however, is soil-dwelling bacteria.

Shen’s lab is focused on a class of natural products called enediynes. These compounds come from bacteria called actinomycetes, which are naturally found in the soil. Two enediyne products are already FDA approved as cancer drugs and are in wide use. But patients who take them often develop resistance. After a period of months or years, tumors can stop responding to the chemotherapy and begin growing again.

While how patients develop resistance to these drugs remains largely unknown, scientists have uncovered two mechanisms that bacteria use to protect themselves from enediynes. “Mechanisms of self-resistance in antibiotic producers serve as outstanding models to predict and combat future drug resistance in a clinical setting,” says Shen.

In the new study, researchers report a third, previously undiscovered resistance mechanism. It involves three genes called tnmS1, tnmS2 and tnmS3, which encode proteins that allow bacteria to resist the effects of a type of enediynes called tiancimycins. Shen’s lab is currently studying tiancimycins, which hold great promise for new cancer drugs. The proteins work by binding to tiancimycins and keeping them separate from the rest of the organism.

After discovering these genes in actinomycetes and how they work, the investigators studied how widespread these genes are in other microorganisms. They were surprised to find that in addition to actinomycetes, the genes were also present in several microorganisms commonly found in the human microbiota, the collection of microorganisms that naturally inhabit the human body.

“This raises a lot of questions that no one has ever asked before,” Shen says. “I can rationalize why the producing organism would have these genes, because it needs to protect itself from its own metabolites. But why do other microorganisms need these resistance genes?” He notes that it may be possible for gut microbes to pass the products of these genes on to their host-;humans-;which could contribute to drug resistance.

“These findings raise the possibility that the human microbiota might impact the efficacy of enediyne-based drugs and should be taken into consideration when developing new chemotherapies,” Shen says. “Future efforts to survey the human microbiome for resistance elements should be an important part of natural product-based drug discovery programs.”

Source:

https://www.scripps.edu/news/press/2018/20180618-chemotherapy-chemistry-cancer.html

Tagged with:

About author

Related Articles