Imagine you’re about to stop on a spot along the way to see local attractions and go on a cross-country trip. I would like to have a road map that covers both major highways and small city and town roads, including maps of various scales, or at least a GPS that can access digital maps using this information. Probably.
Until recently, cancer The researchers were like cross-country travelers, with only a few maps of some popular cities. Also, some cancers grow so rapidly that the map quickly becomes obsolete. This situation has hampered the ability of physicians to understand what is really happening within the tumor and to develop effective treatments.
NS Human Tumor Atlas Network (HTAN) Created to change that. It aims to develop high resolution maps of different types of cancer. This gives doctors a better understanding of the textured terrain of the tumor, including how it changes over time and becomes more deadly. HTAN is funded by the National Cancer Institute and involves a consortium of cancer centers across the United States.
The first such atlas from researchers at the Memorial Sloan Kettering Cancer Center after years of in-depth research- Small cell lung cancer— Now you are ready to view and are full of new insights.
“The most exciting thing we have found is Stem-like cells Within these tumors, which are closely linked to patient outcomes, “explains Charles Rudin, a MSK physician scientist who co-led the lung cancer project. tumor, The prognosis is poor. “
Not only that, these stem-like cells are metastatic, which means they are easy to spread, and researchers have found them across many SCLC tumors that were otherwise very different.
“That was a big surprise,” said Dana Pe’er, a senior researcher at HTAN and a computational biologist at MSK who co-led the Lung Cancer Atlas Project. “This increases the likelihood that this small percentage of cells are promoting metastatic behavior throughout the tumor.”
Small cell lung cancer is one of the most deadly cancers. It tends to spread early and aggressively. Two-thirds of cases are already metastatic at diagnosis. Chemotherapy is not very effective. Researchers hope that the new Atlas, published October 14, 2021, will be published in the journal. cancer cell, Leads to improved care for sick people.
Collaboration leads to new discoveries
Building an atlas required years of collaboration from two groups with very different disciplines. Clinicians like Dr. Rudin with disease-specific expertise in small cell lung cancer, and computational biologists like Dr. Pe’er and his team.
Dr. Rudin points out the fact that there are four co-lead authors in this treatise (a rare event) as evidence of the diversity of skill sets needed to complete such studies. The co-lead authors are Joseph Chan, Álvaro Quintanal-Villalonga, Vianne Ran Gao, and Yubin Xie.
Dr. Pe’er, chair of the Computational and Systems Biology Program at the Sloan Kettering Institute, took the lead in computing things. She is an expert in single-cell RNA seq (scRNAseq). This is a technology that allows scientists to get detailed images of genes that are turned on in hundreds of cells at the same time.
By applying scRNAseq to SCLC tumor specimens from patients with MSK, Dr. Pe’er and her team worked on stem cells lurking within the cells of the surrounding tumor, much like placing a needle on a haystack. We were able to find this rare population of like cells. ..
“We wouldn’t have been able to find these cells in bulk sequencing,” she says. “To find them, we really needed single-cell analysis.” (Bulk sequencing is what researchers do before scRNAseq becomes available. Basically, tumors are blended and dropped. Sequencing all RNA
Focus on molecular changes
Single-cell technology also allowed the team to take it even further. Within the cells that make up this small population, one gene stands out. PLCG2.. This gene makes a protein that acts as a “second messenger.” That is, it relays a signal from one protein to another.
“”PLCG2 Initially, it never attacked me as a gene involved in the regulation of the stem cell population, “says Dr. Rudin.
But surely PLCG2 It seems to play an important role. Scientists have found that this gene is the most highly expressed in this stem cell-like population. And when they experimentally increased or decreased their activity in cancer cell lines, it altered the ability of cancer cells to metastasize.
These are their researchers PLCG2-high cell It may be part of the SCLC aggression description. If so, it may open up new possibilities for treatment.
“It is believed that developing strategies that selectively target this cell population could reduce metastasis and ultimately improve outcomes in patients with small cell lung cancer,” said Dr. Rudin. ..
“What we really want to do is try to stop the transfer on that track,” adds Dr. Pe’er. “But to do that, we need to better understand these rare cell populations that appear to be driving it. That is the goal of this atlas.”
Signs of plasticity, metastasis, and immunosuppression in the atlas of human small cell lung cancer, cancer cell (2021). DOI: 10.1016 / j.ccell.2021.09.008 , www.cell.com/cancer-cell/fullt… 1535-6108 (21) 00497-9
Memorial Sloan Kettering Cancer Center
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