Predicting resistance to anticancer drugs
2021-06-17
(Press-News.org) Cancer cells can develop resistance to therapy through both genetic and non-genetic mechanisms. But it is unclear how and why one of these routes to resistance prevails. Understanding this 'choice' by the cancer cells may help us devise better therapeutic strategies. Now, the team of Prof. Jean-Christophe Marine (VIB-KU Leuven Center for Cancer Biology) shows that the presence of certain stem cells correlates with the development of nongenetic resistance mechanisms. Their study is published in the prestigious journal Cancer Cell.
Two routes to resistance
Even though cancer therapy has made great strides in the last few years, resistance remains a major problem. When cancer cells develop resistance against the drugs targeting them, they can continue to spread, even when the patient is going through therapy.
Until recently, it was thought that this resistance arises exclusively through mutations - genetic alterations - in the cancer cells. However, new studies have suggested that resistance against cancer drugs can also arise via non-genetic mechanisms that change the expression of certain genes without altering the DNA sequence.
Prof. Jean-Christophe Marine (VIB-KU Leuven Center for Cancer Biology): "The importance of nongenetic reprogramming as a driver of therapy resistance is not yet widely accepted in the field. Although my group has demonstrated that drug tolerance can be driven by nongenetic mechanisms, strong evidence that resistance can be acquired in absence of a genetic cause is still lacking."
In their study, the team of Prof. Marine firmly establishes that nongenetic mechanisms contribute to resistance to therapy in melanoma. The key question has become: "How do cancer cells 'choose' between the different routes to resistance?"
Neural crest stem cells as key
Surprisingly, the team demonstrates that the road to resistance is predetermined and not randomly selected. They show that the presence of a specific group of cells, neural crest stem cells, leads to non-genetic rather than genetic drug resistance in melanoma. A possible reason for this is that these neural crest stem cells exhibit 'epigenetic plasticity', which means that these cells have an increased ability to select which genes they express and how much. These cells literally reprogram themselves to evade the therapeutic pressure.
The researchers also identified the signaling pathway that drives the emergence of the neural crest stem cells and promotes their survival. This signaling pathway depends crucially on the protein Focal Adhesion Kinase (or FAK). By blocking the activity of this protein, the team was able to drastically reduce the occurrence of non-genetic drug resistance in patient-derived xenografts - tumor cells from human patients that were implanted in mice.
This combination of new basic insights into tumor cell biology and recently discovered non-genetic resistance mechanisms to cancer drugs has far-reaching clinical consequences.
Florian Rambow, senior postdoc who contributed to the study, explains: "These findings have several important clinical implications. Not only did we show a viable way to suppress non-genetic resistance, but we also demonstrated that the presence of specific cells dictates which resistance mechanism is likely to occur. This observation is the key to predicting potential resistance routes in patients and developing personalized therapies."
INFORMATION:
Publication
Marin-Bejar et al. (2021). Evolutionary predictability of genetic versus nongenetic resistance to anticancer drugs in melanoma. Cancer Cell.
Financing
The KULeuven PDX platform is supported by the Stichting Tegen Kanker grant 2016-054. E.L. is supported by the Melanoma Research Alliance (MRA) Amanda and Jonathan Eilian young investigator award. O.M-B. is supported by 12T1217N project by FWO at the program under the Marie Sk?odowska-Curie grant agreement no. 665501. P.K. received financial support from Marie Curie Individual Fellowship (H2020?MSCA?IF?2018), J.P. received financial support from Marie Curie Individual Fellowship (H2020-MSCA-IF-2019), and J.F. from the Swedish Research Council (Vetenskapsrådet, International postdoc grant, Reg.-Nr.: 2016-00215).
J.D. is supported by a postdoctoral fellowship from FWO (12J6921N). D.P. and N.V.R. received PhD fellowships from the VIB PhD international program and FWO-SB 1S79619N, respectively. This work was supported by FWO (#G.0929.16N), Stichting tegen kanker, Interreg (Skin-Huid), Melanoma Research Alliance (MRA, EIA#623591), KULeuven (C1 grant #C16/19/006) to J-C.M., an OHSU Knight Cancer Center support grant from the National Institutes of Health (NIH P30-CA069533) to A.W.L., Infrastructure grants (type 1 funding from the Hercules Foundation - AKUL/13/41; Foundation Against Cancer project 2015-143) and grants from FWO (I001818N) and KU Leuven C14/18/092 to T.V. and enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council (grant number MR/L016311/1).
Questions from patients
A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.
ELSE PRESS RELEASES FROM THIS DATE:
2021-06-17
African American mothers continue to have the lowest breastfeeding rates, even as the breastfeeding rates have risen in the U.S. over the past 25 years. Racism is an important barrier to breastfeeding, as examined in Part 2 of a special issue on "Breastfeeding and the Black/African American Experience: Cultural, Sociological, and Health Dimensions Through an Equity Lens," published in the peer-reviewed journal Breastfeeding Medicine. Click here to read the issue now.
The special issue is led by Guest Editor Sahira Long, MD, a pediatrician and lactation consultant.
Exploring how racism creates barriers to breastfeeding for Black mothers and how Black women resist racism during their quest to breastfeed are Catasha Davis, PhD and Aubrey Van Kirk Villalobos, DrPH, Milken Institute School ...
2021-06-17
Since 2005, the guidelines for the care of unconscious cardiac arrest patients have been to cool the body temperature down to 33 degrees Celsius. A large, randomised clinical trial led by Lund University and Region Skåne in Sweden has shown that this treatment does not improve survival. The study is published in the New England Journal of Medicine.
"These results will affect the current guidelines", says Niklas Nielsen, researcher at Lund University and consultant in anaesthesiology and intensive care at Helsingborg Hospital, who led the study.
In the early 2000s, two studies in the New England Journal of Medicine showed that induced hypothermia in unconscious cardiac arrest patients ...
2021-06-17
Conservationists have long warned of the dangers associated with bears becoming habituated to life in urban areas. Yet, it appears the message hasn't gotten through to everyone.
News reports continue to cover seemingly similar situations -- a foraging bear enters a neighbourhood, easily finds high-value food and refuses to leave. The story often ends with conservation officers being forced to euthanize the animal for public safety purposes.
Now, a new study by sustainability researchers in the Irving K. Barber Faculty of Science uses computer modelling to look at the best strategies to reduce human-bear conflict.
"It happens all the time, and unfortunately, humans are almost ...
2021-06-17
Research shows that inhibiting necroptosis, a form of cell death, could be a novel therapeutic approach for treating chronic obstructive pulmonary disease (COPD), an inflammatory lung condition, also known as emphysema, that makes it difficult to breathe.
Published in the prestigious American Journal of Respiratory and Critical Care Medicine, the study by a team of Australian and Belgian researchers, revealed elevated levels of necroptosis in patients with COPD.
By inhibiting necroptosis activity, both in the lung tissue of COPD patients as well as ...
2021-06-17
Electrons are ubiquitous among atoms, subatomic tokens of energy that can independently change how a system behaves--but they also can change each other. An international research collaboration found that collectively measuring electrons revealed unique and unanticipated findings. The researchers published their results on May 17 in Physical Review Letters.
"It is not feasible to obtain the solution just by tracing the behavior of each individual electron," said paper author Myung Joon Han, professor of physics at KAIST. "Instead, one should describe or track all the entangled electrons at once. This requires a clever way of treating this entanglement."
Professor Han and the researchers used a recently developed "many-particle" theory to account for the ...
2021-06-17
New UMD study suggests that everywhere tyrannosaurs rose to dominance, their juveniles took over the ecological role of medium-sized carnivores
A new study shows that medium-sized predators all but disappeared late in dinosaur history wherever Tyrannosaurus rex and its close relatives rose to dominance. In those areas--lands that eventually became central Asia and Western North America--juvenile tyrannosaurs stepped in to fill the missing ecological niche previously held by other carnivores.
The research conducted by Thomas Holtz, a principal lecturer in ...
2021-06-17
Like the movie version of Spider-Man who shoots spider webs from holes in his wrists, a little alpine plant has been found to eject cobweb-like threads from tiny holes in specialised cells on its leaves. It's these tiny holes that have taken plant scientists by surprise because puncturing the surface of a plant cell would normally cause it to explode like a water balloon.
The small perennial cushion-shaped plant with bright yellow flowers, Dionysia tapetodes, is in the primula family and naturally occurs in Turkmenistan and north-eastern Iran, and through the mountains of Afghanistan to the border of Pakistan. What makes it unusual is its leaves, which are covered in long silky fibres that ...
2021-06-17
A team of scientists using the Atacama Large Millimeter/submillimeter Array (ALMA) to study the young star Elias 2-27 have confirmed that gravitational instabilities play a key role in planet formation, and have for the first time directly measured the mass of protoplanetary disks using gas velocity data, potentially unlocking one of the mysteries of planet formation. The results of the research are published today in two papers in The Astrophysical Journal.
Protoplanetary disks--planet-forming disks made of gas and dust that surround newly formed young stars--are ...
2021-06-17
Ocean currents sometimes pinch off sections that create circular currents of water called "eddies." This "whirlpool" motion moves nutrients to the water's surface, playing a significant role in the health of the Florida Keys coral reef ecosystem.
Using a numerical model that simulates ocean currents, researchers from Florida Atlantic University's Harbor Branch Oceanographic Institute and collaborators from the Alfred-Wegener-Institute in Germany and the Institut Universitaire Europeen De La Mer/Laboratoire d'Océonographie Physique et Spatiale in France are shedding light on this important "motion of the ocean." They have conducted a first-of-its-kind study identifying ...
2021-06-17
Researchers at the National Institutes of Health have developed a prototype device that could potentially diagnose pregnancy complications by monitoring the oxygen level of the placenta. The device sends near-infrared light through the pregnant person's abdomen to measure oxygen levels in the arterial and venous network in the placenta. The method was used to study anterior placenta, which is attached to the front wall of the uterus. The researchers described their results as promising but added that further study is needed before the device could be used routinely.
The small study was conducted by Amir Gandjbakhche, Ph.D., of the Section on Translational Biophotonics at NIH's Eunice Kennedy Shriver National Institute ...
LAST 30 PRESS RELEASES:
[Press-News.org] Predicting resistance to anticancer drugs
