Scripps Research study provides new clues to improving chemotherapies 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?
June 21, 2018
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.
Other authors of the study, Resistance to Enediyne Antitumor Antibiotics by Sequestration, were Chin-Yuan Chang, Xiaohui Yan, Ivana Crnovcic, Thibault Annaval, Jeffrey D. Rudolf, Dong Yang and Hindra, of Scripps Research, George N. Phillips, Jr. of Rice University, and Changsoo Chang, Boguslaw Nocek, Gyorgy Babnigg and Andrzej Joachimiak of Argonne National Laboratory.
This research was funded by the National Institutes of Health (grants GM098248, GM109456, GM121060, GM094585, CA078747, GM115575 and CA204484) and the Department of Energy, Office of Biological and Environmental Research (grant DE-AC02-06CH11357).
Cancer Chemistry Shen, Ben
Most recent headlines
09/11/2025
Dalet today announced a transformative leap forward for media operations: Agentic Artificial Intelligence (AI) that unifies the Dalet ecosystem under one natura...
23/10/2025
A deadline is looming for a new carriage deal between Verizon's Fios TV and Nexstar, with both Verizon and the pay TV-backed American Television Alliance bl...
23/10/2025
NEW YORK During a high-profile session at NAB Show New York, new survey data was shared that revealed significant public concern over artificial intelligence (A...
23/10/2025
BELLEVUE, Wash. and NEW YORK Fox Weather has tapped T-Mobile has as its preferred communications provider and announced that all Fox Weather reporters are being...
23/10/2025
PBS and Amazon Web Services have announced the network is using generative AI to provide enhanced search results to viewers on the PBS App and PBS LearningMedia...
22/10/2025
Prime Video Inks Deal To Present NFL Black Friday Game Worldwide By SVG Staff
Wednesday, October 22, 2025 - 10:06 am
Print This Story | Subscribe
Story ...
22/10/2025
NBA Tip-Off: ESPN Goes 1080p HDR End-to-End, Flipping HDR Switch on REMI and REM...
22/10/2025
FloSports Empowers Division II, III Athletic Departments With Turnkey Production...
22/10/2025
Wall Street Video Summit Debuts, Bringing Together 200 Financial Enterprise Vide...
22/10/2025
Dueling Pianos: International Chopin Piano Competition Is as Competitive as a Ba...
22/10/2025
In 1995, a young Colombian artist released an album that would change Latin pop ...
22/10/2025
Over the past few months, a photovoltaic system has been installed on a three-he...
22/10/2025
The Orion spacecraft for NASA's Artemis II mission is stacked on the Space Launch System (SLS) rocket in High Bay 3 of the Vehicle Assembly Building at Kenn...
22/10/2025
L3Harris' Hybrid SATCOM is resilient by design, offering path diversity that eliminates vulnerabilities by routing data across the best available networks i...
22/10/2025
WASHINGTON, D.C. Organizers of NAB Show New York said they are expecting more than 12,000 registered attendees from about 100 countries along with 260 exhibitor...
22/10/2025
WASHINGTON, D.C The organizers of The 2025 NAB Show New York have announced that they are expecting more than 12,000 registered attendees from about 100 countr...
22/10/2025
Masque Sound, a leading theatrical sound reinforcement, installation and design company, supplied an extensive gear package of professional-grade equipment for ...
22/10/2025
Lightware, a global leader in signal management and AV connectivity solutions, is seeing strong market momentum for the UCX-3x3-TPX-RX20, a compact transmitter-...
22/10/2025
MELVILLE, N.Y. Chyron has released PAINT 10.2, the latest update for its telestration platform, adding support for SMPTE ST 2110 IP workflows, expanding brandin...
22/10/2025
WASHINGTON Run3TV today said NBCUniversal is joining as an investor in the ATSC 3.0 Framework Authority, which develops the Run3TV NextGen TV application platfo...
22/10/2025
ATLANTA swXtch.io will feature two new networking solutions extending the company's reach across more cloud and on-prem workflows at NAB Show New York, set ...
22/10/2025
The Warner Bros. Discoverys HBO Max streaming services has increased prices for all its streaming tiers effectively immediately for new customers. Existing cust...
22/10/2025
LOS ANGELES OpenDrives has signed a new distribution partnership deal with Versatile Distribution Services (VDS) to strengthen its channel and streamline how it...
22/10/2025
WASHINGTON, D.C The organizers of The 2025 NAB Show New York have announced that they are expecting more than 12,000 registered attendees from about 100 countr...
22/10/2025
Samora Pinderhughes Brings Immersive Sound to Berklee's Signature Series The artist and composer, who's worked with Herbie Hancock, Robert Glasper, Co...
22/10/2025
BMI Day at Berklee Celebrates Composer Fil Eisler and Awards Scholarship to Stud...
22/10/2025
October 22nd, 2025 TRIBECA ANNOUNCES STAR-STUDDED LINEUP OF MEMBERSHIP EVENTS F...
22/10/2025
Rohde & Schwarz and TRUMPF cooperate in drone defense Rohde & Schwarz and TRUMPF partner to deliver a comprehensive drone defense solution combining Rohde & S...
22/10/2025
European Broadcaster Upgrades To Grass Valley's NativeIP LDX 135 Cameras And...
22/10/2025
Everyone Gets a Better Deal on Verizon with New FOX One Perk The $15 FOX One streaming service perk is yet another way Verizon continues to add savings for cu...
22/10/2025
First Look Hidden Assets Series 3
Premieres on 9th November 9:30pm on RT One & RT Player
WATCH HERE Promo Link: Hidden Assets Series 3 | RT
The Crimin...
21/10/2025
NAB New York 2025: Although AES Show Is on Its Own, Audio Will Be a Major Part o...
21/10/2025
NAB New York 2025: Business of Broadcast and Media,' Future of Content'...
21/10/2025
SVG All-Stars: Ethan Folz, Senior Director, Digital Operations and Quality of Ex...
21/10/2025
NBA on NBC/Peacock: Livestream Offers Graphic Overlays, Predictive Gaming, Ancil...
21/10/2025
NBA on NBC/Peacock: At the Front Bench With Producer Frank DiGraci and Director ...
21/10/2025
NBA on NBC/Peacock: NBC Sports, NEP Build Ultra-Flexible Production Plan That Se...
21/10/2025
Indigenous storytelling has been at the heart of the work of the Sundance Instit...
21/10/2025
Top L-R: Mysterious Skin, American Dream Second Row L-R: Little Miss Sunshine, D...
21/10/2025
Last week, Spotify and Columbia Records transformed Pier 4 at the Brooklyn Army ...
21/10/2025
SBS Learn's Dharug Ngurra resource empowers classrooms to meaningfully celeb...
21/10/2025
As global operators simplify and evolve their digital platforms, NPS improvement...
21/10/2025
Critical Design Review completion is a key milestone on the path toward Wideband Global Satellite Communications certification for the network in 2026, opening ...
21/10/2025
New Australian undersea training range to implement and improve warfighting tactics, proficiency and safety; enable joint/allied training that contributes to pr...
21/10/2025
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({...
21/10/2025
September, the beginning of autumn, brought an expected revival to the TV market, largely due to the new fall TV schedules. The time spent in front of the TV sc...
21/10/2025
Broadcast Booms with 20% Uptick vs. August, Achieving Largest Monthly
Increase ...
21/10/2025
During September, streaming's share of TV viewing in Mexico settled at 24.5%, a marginal shift of -0.5 share points from the previous month.
Disclaimer: YU...
21/10/2025
RENNES, France BBright and GlobalM have conducted a technical trial validating Ultra HD interoperability across the entire contribution chain in the cloud, achi...
Scripps Research study provides new clues to improving chemotherapies 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.
