How lung cancer cells disguise themselves to evade chemo data recovery open source

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The disease also has one of the lowest survival rates — partly because lung cancer tumors are either treatment-resistant from the start or they develop resistance to treatment over time.


New research suggests that one reason behind why cancer cells can escape chemotherapy is due to their ability to adopt characteristics of cells from neighboring organs.

What is more, the new study — which was led by purushothama rao tata, an assistant professor of cell biology at duke university school of medicine in durham, NC, and published in the journal developmental cell — finds a genetic mutation and mechanism that drive this shape-shifting process.

On analyzing the genomes of lung cancer tumors, the scientists found that a large number of them lacked NKX2-1.Cancer cells this is a gene known for "telling" cells to develop specifically into a lung cell.

Instead, the team found that these cells had genetic traits normally linked with gastrointestinal organs — such as the pancreas, duodenum, and small intestine — and the esophagus and liver.

Based on these preliminary observations, the scientists hypothesized that knocking out the NKX2-1 gene would make lung cancer cells lose their identity and adopt that of neighboring organs.

So, the researchers tested this hypothesis in two different mouse models. In the first, they depleted the rodents’ lung tissue of the NKX2-1 gene. Doing so made the lung tissue change its appearance and, surprisingly, its behavior.Lung cancer

A microscopic analysis of the lung tissue revealed that it had started to resemble gastric tissue in its structure, as well as produce digestive enzymes.

Next, prof. Tata and team wondered what would happen if they activated two oncogenes: SOX2 and KRAS. Triggering the former led to tumors that looked as though they resided in the foregut, while activating the latter caused tumors that looked as if they were in the mid- and hindgut.

Together, the authors conclude, "these findings demonstrate that elements of pathologic tumor plasticity mirror the normal developmental history of organs in that cancer cells acquire cell fates associated with developmentally related neighboring organs."

Cancer cells

Prof. Tata, who is also a member of the duke cancer institute, explains what the findings mean for understanding how lung cancer might develop chemotherapy resistance.

"Cancer cells will do whatever it takes to survive," he explains. "Upon treatment with chemotherapy, lung cells shut down some of the key cell regulators and pick up the characteristics of other cells in order to gain resistance."

"Cancer biologists have long suspected that cancer cells could shape-shift in order to evade chemotherapy and acquire resistance, but they didn’t know the mechanisms behind such plasticity."

"Now that we know what we are dealing with in these tumors," he adds, "we can think ahead to the possible paths these cells might take and design therapies to block them."

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