- Press Release Distribution

Target growth-driving cells within tumors, not fastest-proliferating cells

Target growth-driving cells within tumors, not fastest-proliferating cells
( BOSTON –– Of the many sub-groups of cells jockeying for supremacy within a cancerous tumor, the most dangerous may not be those that can proliferate the fastest, researchers at Dana-Farber Cancer Institute report in a paper appearing in an advance online publication of the journal Nature. The findings have important implications for the treatment of cancer with precision medicines, the study authors explained: Doctors need to ascertain which cell subgroups are truly driving the tumor's growth and metastasis and select drugs that target the critical genes within those cells. It can be a mistake to assume that the largest, most dominant subgroup is the one to be targeted.

"It is well-established that individual tumors are genetically heterogeneous – comprised of multiple subgroups of cancer cells, each with its own genomic signature, or pattern of gene mutations," said the study's senior author, Kornelia Polyak, MD, PhD, of Dana-Farber. "We wanted to explore the factors that allow these subgroups to coexist, and to understand why the subgroup with the greatest proliferative ability does not always take over the tumor."

It has been long assumed that mutations that speed up the proliferation of cancer cells are also responsible for tumor growth. Indeed, when the growth of tumor cells is unchecked (as occurs in lab-grown tumor cells), the subgroup that proliferates fastest should outgrow other subgroups. In actual tumors, however, cell growth is constrained by limited access to environmental factors such as space, nutrients, and oxygen. As a result, tumors often grow much slower than they would under laboratory conditions. The presence of fast-growing cells does not necessarily cause tumors to enlarge, because their fast growth rates are offset by higher rates of cell death. If a subgroup of cancer cells "figures out" how to change the tumor environment so some of the restraints on tumor growth are removed, that subgroup may have a competitive advantage over other subgroups within the tumor.

To simulate what happens within cancer patients, investigators implanted breast cancer samples in laboratory animals. One set of samples produced tumors that grew very slowly, even though the cells within them were proliferating rapidly, suggesting the tumors were constrained by environmental factors. Researchers used these growth-stunted tumors to generate several subgroups of cancer cells, each of which overproduced a different protein linked to tumor growth.

The investigators then ran a series of tests in which they implanted in mice a single subgroup plus the original cell sample or a mix of several subgroups and observed the growth of the resulting tumors. They found that two of the sub-groups – one overproducing a protein called CCL5, the other overproducing a protein called IL11 – were able to drive tumor growth out of the gridlock.

"Surprisingly, there was no link between a subgroup's ability to drive tumor growth and its competitive expansion within the tumor," remarked Polyak, who is also a Professor of Medicine at Harvard Medical School and an associate at the Broad Institute of MIT and Harvard. The subgroup overproducing IL11 was able to increase tumor growth by relieving environmental constraints, even though the subgroup didn't gain a competitive advantage from this ability, since other subgroups benefited as well. On the other hand, a subgroup that overproduced the protein LOXL3 took over a large share of the tumor but could not increase overall tumor growth. Interestingly, when investigators implanted tumors composed of the IL11 and LOXL3 subgroups, the tumors grew very fast, but the IL11 subgroup was eventually outcompeted by LOXL3 subgroup, leading to collapse of the tumor as environmental constraints were restored.

Investigators found that when multiple subgroups were present in the same tumor, they interfered with each other's expansion. This suggests that once heterogeneity arises within a tumor, it tends to persist, as it becomes difficult for a single subgroup to take over the tumor, the study authors state. Such co-existence allows interactions between the various subgroups to take place. Indeed, investigators found that when multiple subgroups are present in the same tumors, the tumors grow faster and also become metastatic, which hasn't been observed in tumors composed of any single subgroup.

"The goal of precision therapy for cancer is to kill the subsets of cells that are driving the tumor's growth – even if other subsets are proliferating more robustly," Polyak explained. Targeting the fast-proliferating subsets could actually be harmful, she continued: by removing a competitor, such drugs could assist the growth-driving subsets, thereby enhancing growth of the overall tumor. "We need to be sure we're targeting the actual drivers."

INFORMATION: Funding for the study was provided by the Dana-Farber Cancer Institute Physical Sciences-Oncology Center; the CDMRP Breast Cancer Research Program; Cellex Foundation; Deutsche Akademie der Naturforscher Lepoldina; and the Breast Cancer Research Foundation.

The lead authors of the study are Andriy Marusyk, PhD, and Doris Tabassum, of Dana-Farber and Harvard Medical School. Co-authors are Franziska Michor, PhD, and Philipp Altrock, PhD, of Dana-Farber and the Harvard School of Public Health; and Vanessa Almendro, PhD, of Dana-Farber and Harvard Medical School.

About Dana-Farber Cancer Institute Dana-Farber Cancer Institute, a principal teaching affiliate of Harvard Medical School, is world-renowned for its leadership in adult and pediatric cancer treatment and research. Designated as a comprehensive cancer center by the National Cancer Institute (NCI), it is one of the largest recipients among independent hospitals of NCI and National Institutes of Health grant funding. For more information, go to

Contact: Teresa Herbert or Robert Levy, Dana-Farber Cancer Institute;; 617-632-4090

[Attachments] See images for this press release:
Target growth-driving cells within tumors, not fastest-proliferating cells


ALMA finds double star with weird and wild planet-forming discs

ALMA finds double star with weird and wild planet-forming discs
BOWLING GREEN, O.—From movies to television, obesity is still considered "fair game" for jokes and ridicule. A new study from researchers at Bowling Green State University took a closer look at weight-related humor to see if anti-fat attitudes played into a person's appreciation or distaste for fat humor in the media. "Weight-Related Humor in the Media: Appreciation, Distaste and Anti-Fat Attitudes," by psychology Ph.D. candidate Jacob Burmeister and Dr. Robert Carels, professor of psychology, is featured in the June issue of Psychology of Popular Media Culture. Carels ...

Innovative scientists update old-school pipetting with new-age technology

Innovative scientists update old-school pipetting with new-age technology
CAMBRIDGE, Mass. (July 30, 2014) A team of Whitehead Institute researchers is bringing new levels of efficiency and accuracy to one of the most essential albeit tedious tasks of bench science: pipetting. And, in an effort to aid the scientific community at large, the group has established an open source system that enables anyone to benefit from this development free of charge. Dubbed "iPipet," the system converts an iPad or any tablet computer into a "smart bench" that guides the execution of complex pipetting protocols. iPipet users can also share their pipetting designs ...

Mapping the optimal route between 2 quantum states

Mapping the optimal route between 2 quantum states
As a quantum state collapses from a quantum superposition to a classical state or a different superposition, it will follow a path known as a quantum trajectory. For each start and end state there is an optimal or "most likely" path, but it is not as easy to predict the path or track it experimentally as a straight-line between two points would be in our everyday, classical world. In a new paper featured this week on the cover of Nature, scientists from the University of Rochester, University of California at Berkeley and Washington University in St. Louis have shown ...

Young binary star system may form planets with weird and wild orbits

Young binary star system may form planets with weird and wild orbits
Unlike our solitary Sun, most stars form in binary pairs -- two stars that orbit a common center of mass. Though remarkably plentiful, binaries pose a number of questions, including how and where planets form in such complex environments. While surveying a series of binary stars with the Atacama Large Millimeter/submillimeter Array (ALMA), astronomers uncovered a striking pair of wildly misaligned planet-forming disks in the young binary star system HK Tau. These results provide the clearest picture ever of protoplanetary disks around a double star and could reveal important ...

Scientists reproduce evolutionary changes by manipulating embryonic development of mice

A group of researchers from the University of Helsinki and the Universitat Autònoma de Barcelona have been able experimentally to reproduce in mice morphological changes which have taken millions of years to occur. Through small and gradual modifications in the embryonic development of mice teeth, induced in the laboratory, scientists have obtained teeth which morphologically are very similar to those observed in the fossil registry of rodent species which separated from mice millions of years ago. To modify the development of their teeth, the team from the Institute ...

Conservation scientists asking wrong questions on climate change impacts on wildlife

Scientists studying the potential effects of climate change on the world's animal and plant species are focusing on the wrong factors, according to a new paper by a research team from the Wildlife Conservation Society, University of Queensland, and other organizations. The authors claim that most of the conservation science is missing the point when it comes to climate change. While the majority of climate change scientists focus on the "direct" threats of changing temperatures and precipitation after 2031, far fewer researchers are studying how short-term human adaptation ...

Antarctic ice sheet is result of CO2 decrease, not continental breakup

DURHAM, N.H. – Climate modelers from the University of New Hampshire have shown that the most likely explanation for the initiation of Antarctic glaciation during a major climate shift 34 million years ago was decreased carbon dioxide (CO2) levels. The finding counters a 40-year-old theory suggesting massive rearrangements of Earth's continents caused global cooling and the abrupt formation of the Antarctic ice sheet. It will provide scientists insight into the climate change implications of current rising global CO2 levels. In a paper published today in Nature, Matthew ...

NASA catches two tropical troublemakers in Northwestern Pacific: Halong and 96W

NASA catches two tropical troublemakers in Northwestern Pacific: Halong and 96W
There are two tropical low pressure areas in the Northwestern Pacific Ocean today and they're close enough to each other to be captured in one image generated from data gathered by NASA's Aqua satellite. NASA's Aqua satellite flew over both Tropical Storm Halong and developing System 96W early on July 30 and the Atmospheric Infrared Sounder (AIRS) instrument captured infrared data on them in one image. Both systems show powerful thunderstorms stretching high into the troposphere with cloud top temperatures as cold as -63F/-52C. Those thunderstorms have the potential for ...

Watching Schrödinger's cat die (or come to life)

Watching Schrödingers cat die (or come to life)
One of the famous examples of the weirdness of quantum mechanics is the paradox of Schrödinger's cat. If you put a cat inside an opaque box and make his life dependent on a random event, when does the cat die? When the random event occurs, or when you open the box? Though common sense suggests the former, quantum mechanics – or at least the most common "Copenhagen" interpretation enunciated by Danish physicist Neils Bohr in the 1920s – says it's the latter. Someone has to observe the result before it becomes final. Until then, paradoxically, the cat is both dead and ...

Fear of losing money, not spending habits, affects investor risk tolerance, MU study finds

As the U.S. economy slowly recovers, many investors remain wary about investing in the stock market. Investors' "risk tolerance," or their willingness to take risks, is an important factor for investors deciding whether, and how much, to invest in the stock market. Now, Michael Guillemette, an assistant professor of personal financial planning in the University of Missouri College of Human Environmental Sciences, along with David Nanigian, an associate professor at the American College, analyzed the causes of risk tolerance and found that loss aversion, or the fear of losing ...


Unveiling the mysteries of cell division in embryos with timelapse photography

Survey finds loneliness epidemic runs deep among parents

Researchers develop high-energy-density aqueous battery based on halogen multi-electron transfer

Towards sustainable food systems: global initiatives and innovations

Coral identified as oldest bioluminescent organism, suggesting a new model of ancient ecology

SRI chosen by DARPA to develop next-generation computational design of metallic parts and intelligent testing of alloys

NJIT engineers muffle invading pathogens with a 'molecular mask'

Perinatal transmission of HIV can lead to cognitive deficits

The consumption of certain food additive emulsifiers could be associated with the risk of developing type 2 diabetes

New cancer research made possible as Surrey scientists study lipids cell by cell 

Bioluminescence first evolved in animals at least 540 million years ago

Squids’ birthday influences mating

Star bars show Universe’s early galaxies evolved much faster than previously thought

Critical minerals recovery from electronic waste

The move by Apple Memories to block potentially upsetting content illustrates Big Tech’s reach and limits, writes Chrys Vilvang

Chemical tool illuminates pathways used by dopamine, opioids and other neuronal signals

Asian monsoon lofts ozone-depleting substances to stratosphere

PET scans reveal ‘smoldering’ inflammation in patients with multiple sclerosis

Genetics predict type 2 diabetes risk and disparities in childhood cancer survivors

Health information on TikTok: The good, the bad and the ugly

New study points to racial and social barriers that block treatment for multiple myeloma

Rensselaer researcher finds that frog species evolved rapidly in response to road salts

A new chapter in quantum vortices: Customizing electron vortex beams

Don’t be a stranger – study finds rekindling old friendships as scary as making new ones

There’s no ‘one size fits all’ when it comes to addressing men’s health issues globally

Comparison of the “late catch-up” phenomenon between BuMA Supreme and XIENCE stents through serial optical coherence tomography at 1–2 month and 2 year follow-ups: A multicenter study

Marine plankton communities changed long before extinctions

Research reveals tools to make STEM degrees more affordable

Q&A: UW research shows neural connection between learning a second language and learning to code

Keane wins 2024 Gopal K. Shenoy Excellence in Beamline Science Award

[] Target growth-driving cells within tumors, not fastest-proliferating cells