Nav: Home

Novel mathematical framework provides a deeper understanding of how drugs interact

November 13, 2019

Combining two or more drugs can be an effective treatment of diverse diseases, such as cancer. Yet, at the same time, the wrong drug combination can cause major side effects. Currently there is no systematic understanding of how different drugs influence each other. Thus, elucidating how two given drugs interact, and whether they have a beneficial effect, would mean a major step towards drug development to treat diseases more effectively in the future.

On a molecular level, drugs cause complex perturbations of various cellular processes in our body. These processes are orchestrated by an intricate network of molecular interactions, the so-called interactome. Over the last decade, numerous studies have revealed a close relationship between the structure of the interactome and the functional organization of the molecular machinery within the cell. This opened exciting opportunities for using network-based approaches to investigate the foundations of both healthy and disease states. Following this trend, Principal Investigator Jörg Menche and his group at CeMM developed a novel mathematical framework for mapping out precisely how different perturbations of the interactome influence each other.

The new study performed by Caldera et al., represents the first general approach to quantifying with precision how drugs interact with each other, based on a mathematical model that considers their high-dimensional effects. Their research reveals that the position of targets of a given drug on the interactome is not random but rather localized within so-called drug modules. They found that the location of a drug module is linked to the specific cell morphological changes induced by the respective treatments, making morphology screens a valuable resource for the investigation of drug interactions. Further they identified various factors that contribute to the emergence of such interactions. Most notably, the distance between two drug modules on the interactome plays a key role: Certain types of interactions are more likely depending on the exact proximity between the two respective drug modules. If the modules are too far away from each other, it is rather unlikely that an interaction will take place.

"We developed a completely new methodology to classify drug interactions. Previous methods could characterize interactions only as synergistic or antagonistic. Our methodology is able to distinguish 12 distinct interactions types and also reveals the direction of an interaction", says Michael Caldera, first author of the study and PhD student at Jörg Menche's Group.

The study of the Menche group has broadened the understanding of how drugs perturb the human interactome, and what causes drugs to interact. Moreover, the introduced methodology offers the first comprehensive and complete description of any potential outcome that may arise from combining two perturbations. Finally, this methodology could also be applied to address other key challenges, such as dissecting the combined impact of genetic variations or predicting the effect of a drug on a particular disease phenotype. Their research forms a solid base for understanding and developing more effective drug therapies in the future.
-end-


CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

Related Drugs Articles:

Wallflowers could lead to new drugs
Plant-derived chemicals called cardenolides - like digitoxin - have long been used to treat heart disease, and have shown potential as cancer therapies.
Bristol pioneers use of VR for designing new drugs
Researchers at the University of Bristol are pioneering the use of virtual reality (VR) as a tool to design the next generation of drug treatments.
Towards better anti-cancer drugs
The Bayreuth biochemist Dr. Claus-D. Kuhn and his research team have deciphered how the important human oncogene CDK8 is activated in cells of healthy individuals.
Separating drugs with MagLev
The composition of suspicious powders that may contain illicit drugs can be analyzed using a quick and simple method called magneto-Archimedes levitation (MagLev), according to a new study published in the journal Angewandte Chemie.
People are more likely to try drugs for the first time during the summer
American teenagers and adults are more likely to try illegal or recreational drugs for the first time in the summer, a new study shows.
Drugs used to enhance sexual experiences, especially in UK
Combining drugs with sex is common regardless of gender or sexual orientation, reveals new research by UCL and the Global Drug Survey into global trends of substance-linked sex.
Promising new drugs for old pathogen Mtb
UConn researchers are targeting a metabolic pathway, the dihydrofolate reductase pathway, crucial for amino acid synthesis to treat TB infections.
Can psychedelic drugs heal?
Many people think of psychedelics as relics from the hippie generation or something taken by ravers and music festival-goers, but they may one day be used to treat disorders ranging from social anxiety to depression, according to research presented at the annual convention of the American Psychological Association.
New uses for existing antiviral drugs
Broad-spectrum antiviral drugs work against a range of viral diseases, but developing them can be costly and time consuming.
New TB drugs possible with understanding of old antibiotic
Tuberculosis, and other life-threatening microbial diseases, could be more effectively tackled with future drugs, thanks to new research into an old antibiotic by the University of Warwick and the Francis Crick Institute.
More Drugs News and Drugs Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.