Health
Scientists reveal fundamental changes in cancer treatment and understanding
San Francisco-Scientists are potential therapeutic targets by understanding cancer and mapping disease-causing protein groups, according to three groundbreaking papers published together Thursday in the scientific journal. Both of the numbers have been greatly expanded.
A treatise representing nearly 10 years of work Dozens of scientists have been involved for the first time to show how hundreds of different interactions between proteins contribute to breast and head and neck cancer.
In addition, according to Nevan Krogan, a researcher at the University of California, San Francisco, protein group mapping strategies can be used for all known cancers, and pharmaceutical companies look for existing drugs that may also serve as cancer treatments. Should be useful for. Long-term new drugs may also be developed.
Krogan co-directed three studies with Trey Ideker, a professor at the University of California, San Diego, as part of a $ 20 million project called the Cancer Cell Mapping Initiative.
In 2020, Crogan and collaborators around the world A series of attention-grabbing COVID-19 studies.. Studies conducted after the lab shifted its focus to pandemics have led to more than 20 clinical trials of possible therapies.
He and other scientists see similar possibilities in discovering new cancers.
In an interview with the Milwalky Journal Sentinel, Crogan, who heads the UCSF Institute for Quantitative Biological Sciences, said, “Large and small pharmaceutical companies will consider these maps.”
“This is a very comprehensive and novel conceptualization of thinking about genetic data and cancer genomics,” said Eric Fisher, a senior researcher at the Dana-Farber Cancer Institute in Boston, who was not involved in the new research. rice field.
“I think this is what many people think, but as far as I know, this is the first example of putting information in such a comprehensive context.”
Overall, cancer is the country’s second leading cause of death after heart disease, killing more than 600,000 Americans each year. The National Institutes of Health estimates that approximately 1.9 million Americans will be diagnosed with cancer in 2021.
Related:Answer six important questions about these groundbreaking cancer studies.
Three treatises (one for breast cancer, one for head and neck cancer, and one for explaining mapping techniques) represent a fundamental shift in the scientific approach to the disease.
The change began in 2003 with the decoding of our genetic blueprint, the human genome. At the time, Scientists wanted a genome It turns out that most cancers are caused by a defect in one of our 20,000 genes. Repair defects, theoretically You stop the illness..
For this reason, many researchers have spent decades investigating one or two genes.
However, the situation of cancer emerging from the human genome has turned out to be much more complex and treatments are more elusive.
Genes have instructions for making proteins, but it is the proteins themselves that carry out every action in human life, from speaking and growing to breathing and even thinking.
Krogan and his collaborators focused on the community of proteins involved in cancer. Some are as small as two, while others have up to 100 proteins working together.
In breast cancer studies, scientists compared three different cell lines: two different types of tumor cells and one healthy cell. They used the same combination to study head and neck cancer.
“What these treatises are doing is a more comprehensive understanding of the idea that cancer is a disease of network defects,” explains Raghu Kalluri, chair of cancer biology at the MD Anderson Cancer Center in Houston. Did.
“Twenty years ago, we didn’t understand the complexity of the number of defects that cancer cells are accumulating. There may be some mutated genes in general, but cancer cells do. Can carry a lot of flaws. It’s much more complicated than we knew. “
In a new treatise, Crogan and his colleagues describe nearly 600 different protein interactions in breast cancer, nearly 80% of which have not been previously reported. They detail over 700 protein interactions in head and neck cancer. So far, 84% have not been reported.
But this complexity also brings new hope.
An important finding in the study is that there are ways to stop the machines that cause far more cancer than previously thought.
For example, if a group of 10 proteins work together to cause a particular cancer, scientists do not have to limit the target to two or three defective. Instead, they can stop the carcinogenic machine by neutralizing any of the 10 proteins in the community.
Studies also suggest ways that may solve the disease’s ability to develop resistance to certain treatments, one of the most frustrating problems with cancer.
The new map raises the possibility that doctors may be able to stay one step ahead of cancer by giving patients a cocktail of medicines. Some drugs may block a group of proteins that pursue one pathway to cancer, while others block another.
Krogan and his colleagues have identified some particularly promising proteins for treatment, such as spinophylline for breast cancer and Daple for head and neck cancer.
At the Dana-Farber Cancer Institute, Fisher said protein mapping does not mean the end of treatment that patients are accustomed to — surgery, chemotherapy, and radiation therapy. Understanding the specific protein mechanisms that cause cancer in humans is expected to allow doctors to choose the chemotherapeutic agents that are most likely to defeat them.
“There’s one thing to watch out for,” Fisher added. “These are currently the first studies. We didn’t bring them to the patient.”
Researchers also tested two types of tumor cells for each cancer, but said they were “minor” compared to the true diversity found in tumors, according to the Deputy Director of Cancer Biology at the National Cancer Institute. One Shannon Hughes says. Different patients have tumor cells that are characterized by different combinations of defects.
Nonetheless, Hughes called the study “an important step in understanding the more general principles of cancer.”
And it’s not just cancer.
“This will change our view of the disease,” Crogan said.
Largely different diseases such as breast cancer and schizophrenia may involve several of the same proteins due to the overlapping protein communities. A single protein can play a role in two or three different communities, each performing a different function within the cell.
Crogan and his colleagues are already planning to develop a protein-protein interaction map that provides a window to the internal workings of autism, Alzheimer’s disease, and Parkinson’s disease.
Images of the various proteins that work together in a group form the appropriate metaphor for the work required to complete a large mapping project.
One of the hallmarks of the research by Krogan and his colleagues is the collaboration between multiple laboratories. Cancer treatises included contributions from the Rutgers Cancer Institute at Oregon Health & Science University, the J. David Gladstone Institutes at San Francisco, and the University of California at San Diego.
One of Crogan’s COVID-19 treatises, published in Science a year ago, lists about 200 authors, including a group at the Pasteur Institute in Paris. European Bioinformatics Institute in Cambridge, England. Freiburg University in Germany. The University of Sheffield, England. Mount Sinai School of Medicine in New York. Gladstone Institutes in San Francisco.
“One of the really important things is the joint aspect of these studies,” said Hughes of the National Cancer Institute. “It contains many different expertises, which require team science.”
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