Scientists at Stanford Medicine have determined that cells destined to become cancerous undergo a sequence of explicit and foreseeable genetic modifications years prior to reaching a pre-malignant state. This groundbreaking research paves the way for earlier diagnostic procedures and therapeutic interventions, possibly halting the evolution of cancer in its initial phases.
Predictable Genetic Sequences Map Cancer’s Trajectory
The team at Stanford Medicine has ascertained that prospective cancer cells accrue genetic alterations in an ordered and predictable fashion long before they manifest as pre-malignant conditions. Many of these genetic modifications impact cellular pathways that govern cell division, structural integrity, and intracellular communication, priming the cells for malignant transformation well before any overt signs or symptoms become apparent.
This research represents the inaugural comprehensive examination of the nascent stages of human cancer evolution, commencing with cells containing a single mutation conducive to cancer and concluding with a lineage of descendant cells laden with a multitude of genetic irregularities.
The early identification of steps leading to eventual cancer development could not only permit unprecedentedly early diagnosis—when the lethal manifestation is merely nascent—but may also pinpoint innovative interventions to halt the disease’s advancement, the scientists contend.
“Optimally, we aim to halt this progression before the cells transition into a full-blown cancerous state,” commented Christina Curtis, Ph.D., Professor of Medicine, Genetics, and Biomedical Data Science. “Is it possible to identify a minimal set of genetic variations that signify a cell’s impending malignant progression? The consistent nature of the genetic alterations we’ve observed across multiple donors suggests that such identification may indeed be feasible.”
Curtis serves as the senior author of the research, published on May 31 in the scientific journal Nature. Leading the study were former postdoctoral scholar Kasper Karlsson, Ph.D., and visiting graduate student Moritz Przybilla.
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Cells with Inauspicious Origins
The study expands on earlier work conducted in Curtis’s lab, which suggested that some cells in colon cancer were inherently predisposed to metastasize long before the disease could be detected.
“Our analyses of established tumors indicated that early genomic alterations set the course for future developments, many of which transpire before the formation of tumors,” Curtis elaborated. “We aimed to explore what occurs at the absolute earliest stages. Can we anticipate the evolutionary path of a cancer cell? Is the outcome repeatable under identical initial conditions?”
The team examined minuscule three-dimensional aggregations of human stomach cells, termed gastric organoids, acquired from patients undergoing gastric bypass surgeries for obesity treatment. At the study’s outset, a key cancer-related protein called p53 was deactivated to provoke the cells toward malignancy. Known mutations in p53 are a precursor to many human cancers, instigating an array of additional genetic variations including mutations and alterations in the number of genome copies during cell division.
The Observational Period
For a span of two years, at fortnightly intervals, Karlsson documented the genetic shifts in the dividing cells. When analyzed, although changes seemed to occur randomly, those that conferred superior adaptability granted their host cells a competitive edge over other cells within the organoid. Repetitive cycles of mutation and competition revealed discernable patterns.
Discernible Genetic Pathways
“Certain genome regions are consistently eradicated shortly after the initial deactivation of p53,” Curtis noted. “These were observed repeatedly in cells from both the same and different donors. This implies an intrinsic cellular hardwiring into tumor evolution, despite these cells appearing largely normal when observed microscopically; they have yet to evolve into cancer.”
The team found these early alterations typically occur in biological pathways that regulate cell division frequency, disrupt a cell’s elaborate internal signaling mechanism, or control cell structural orientation and spatial positioning within a tissue.
Similar patterns were recurrently observed in cells from various donors. These changes parallel mutations previously identified in stomach cancer and Barrett’s esophagus, a precancerous condition.
“Certain constraints in the system result in a degree of predictability at both the genomic and transcriptomic levels, providing insights into the origins of these cancers,” Curtis added.
Future research plans include repeating the study with alternative cell types and different initiating mutations.
Reference and Contributions
The study, titled “Deterministic evolution and stringent selection during preneoplasia,” was authored by a team led by Christina Curtis and published in Nature on May 31, 2023. Contributions were also made by researchers from Karolinska Institutet, University College London, and the Chan Zuckerberg Biohub.
Funding for this research was provided by the National Institutes of Health (grants DP1-CA238296 and U01-CA217851) and the Swedish Research Council.
Frequently Asked Questions (FAQs) about Cancer Genesis
What is the main finding of the Stanford Medicine researchers?
The main finding of the Stanford Medicine researchers is that cells destined to become cancerous undergo a sequence of explicit and foreseeable genetic alterations years prior to reaching a pre-malignant state. These discoveries could allow for earlier diagnosis and more targeted interventions in cancer treatment.
Who is the senior author of this research?
The senior author of this research is Christina Curtis, Ph.D., who is a Professor of Medicine, Genetics, and Biomedical Data Science at Stanford.
What methodology was used in this study?
The researchers used three-dimensional aggregations of human stomach cells, known as gastric organoids, which were obtained from patients undergoing gastric bypass surgeries. The key cancer-associated protein p53 was deactivated at the study’s outset to provoke the cells toward malignancy. Genetic changes in these cells were monitored every two weeks over a period of two years.
What do the researchers aim to do next?
The researchers plan to replicate this study with different types of cells and different initiating events other than p53 mutations. They also aim to delve into the relationship between host cells and their environment, including potential roles of inflammatory factors in cancer progression.
What is the significance of predictable genetic alterations?
The predictability of these genetic alterations suggests that it might be possible to identify a minimal set of genetic variations that signify a cell’s impending progression to a malignant state. This could pave the way for earlier and more precise diagnosis as well as targeted therapeutic interventions.
Was the research funded? If so, by whom?
Yes, the research was funded by the National Institutes of Health (grants DP1-CA238296 and U01-CA217851) and the Swedish Research Council.
Were there other institutions involved in this research?
Yes, researchers from Karolinska Institutet, University College London, and the Chan Zuckerberg Biohub also contributed to the study.
When and where was this study published?
The study was published on May 31, 2023, in the scientific journal Nature.
What are the implications for cancer treatment?
The implications for cancer treatment could be profound, particularly in the area of early diagnosis and prevention. The study points towards the possibility of intercepting the cancerous progression of cells at its earliest stages, thereby potentially halting the disease before it advances.
Do the researchers believe the findings are universally applicable?
While the research showed consistent genetic alterations across multiple donors, the scientists plan to conduct further studies with different cell types and initiating events to ascertain the universality of these findings.
More about Cancer Genesis
- Stanford Medicine Research Overview
- Nature Journal
- National Institutes of Health Grants
- Swedish Research Council
- Karolinska Institutet
- University College London
- Chan Zuckerberg Biohub
- Understanding Cancer Genetics
- Early Cancer Diagnosis
- Role of p53 in Cancer
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8 comments
So the research was funded by NIH and Swedish Research Council huh? Hope they pour more funds into this. Deserves all the support it can get.
Absolutely brilliant work! The thought that doctors might one day be able to stop cancer before it starts is mind-blowing. Kudos to the team!
Im amazed by the level of detail theyve gone into. Tracking changes every two weeks for two years? Thats dedication right there!
very interesting to see they’ve studied this on stomach cells. Wonder how it will translate to other types of cells and cancers.
if this can lead to early detection, were talking about potentially saving millions of lives. just incredible!
Wow, this is a game changer in cancer research. Can’t believe they can now predict the changes in cells way before they turn into cancer. This is huge!
This study seems groundbreaking. Its high time we found better ways to catch cancer early on, and it looks like we’re finally getting there!
What’s next? Would be fascinating to see how they apply this to practical diagnosis and treatments. Waiting to hear more about this.