Why is cancer deadly?

▎Editor of WuXi AppTec's content team When it comes to cancer, many people's first impression is that it is fatal
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However, in many cases, there is no clear answer as to what is the cause of death from cancer
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For example, if cancers occur in non-vital organs such as the skin, why does it kill people? According to Professor David Bilder, a biologist at UC Berkeley, although cancer metastasis is often cited by doctors as a leading cause of cancer death, this does not answer the fundamental question
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To give a simple example: "If the tumor metastasizes to the lungs, does the patient die from lung failure or from other problems?" Image source: 123RF researchers use "paraneoplastic syndromes" to summarize those It is not directly related to the tumor but can cause systemic symptoms
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Cachexia is a typical state of systemic exhaustion, which causes cancer patients to become increasingly thinner, even through intravenous infusion of nutrients
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Professor Bilder's research team has discovered a possible cause of cachexia.
Chemical substances released by cancer cells can hinder the function of insulin
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In addition, other studies have pointed out that other substances produced by cancer cells may also cause other systemic problems and ultimately lead to death of patients
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In a new study recently published in the academic journal Developmental Cell, Professor Bilder's team has made a new discovery: a cytokine produced by malignant tumors can cause the blood-brain barrier to leak and accelerate death
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The researchers thus pointed out a new anti-cancer strategy-dealing with the impact of the tumor, rather than killing the tumor itself
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This strategy has been initially verified in animal experiments: blocking the destruction of the blood-brain barrier by cytokines can improve the health of cancer-bearing animals and prolong their lives
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▲ Schematic diagram of the study (picture source: reference [1]) It is worth mentioning that the discovery of Professor Bilder's team came from fruit flies, an insect that sounds far away from humans
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"We described 20 years ago that fruit flies grow tumors similar to humans," said Professor Bilder.
"Now we are also seeing that in cachexia, blood coagulation dysfunction, immune response, cytokine production, etc.
, The tumor host response of Drosophila is also significantly similar to that of humans
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"Using the Drosophila cancer model, researchers found that the cytokine interleukin-6 (IL-6) released by malignant tumors can extensively activate JAK-STAT in host cells.
Signal transduction accelerates the death of fruit flies
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The STAT activity is particularly high in the cells that constitute the blood-brain barrier, and causes an abnormal increase in the permeability of the blood-brain barrier
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▲A cross-section of the brain of a fruit fly.
After the blood-brain barrier is broken, the blood-derived substance (green) penetrates into the brain tissue (Image source: Reference [2]; Image: Dr.
Jung Kim) Based on clues found in fruit flies, research The staff continued to verify in the mouse model
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The experimental results also showed that IL-6 released by tumors would also destroy the blood-brain barrier of mice
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"The cytokine IL-6 is known to cause inflammation
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But our new discovery is that this inflammation caused by tumors can also lead to leakage of the blood-brain barrier
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" Professor Bilder emphasized
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Researchers used IL-6 receptor blockers to block the activity of IL-6 on the blood-brain barrier and found that it can extend the lifespan of cancer-bearing fruit flies by 45%
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Similar results were also observed in mouse experiments
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Three weeks after receiving IL-6 receptor blocker treatment, 75% of cancer mice were alive, compared with 25% of untreated cancer mice
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▲Drosophila (upper row) and mice (lower row).
Cytokines released by tumors to the whole body cause blood-brain barrier leakage (picture source: reference [2]; Credit: Jung Kim and Hsiu-Chun Chuang) However, It's not just the destruction of the blood-brain barrier that kills animals
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Researchers noticed that fruit flies without tumors can survive for three to four weeks if the blood-brain barrier leaks, but when they have tumors, they die almost immediately after the blood-brain barrier is damaged
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"We speculate that the tumor also causes other problems.
Maybe it releases certain substances into the circulation and then crosses the broken barrier into the brain; or conversely, something enters the blood from the brain
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" The researchers pointed out
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Image source: Professor 123RF Bilder's team has found some other chemicals released by malignant tumors through Drosophila cancer models, which may be related to tumor-associated syndromes such as edema or hypercoagulability
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These clues need more follow-up research work to verify
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We look forward to the work of scientists to find more potential ways to improve the survival of cancer patients
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Reference: [1] Jung Kim et al.
, (2021) Tumor-induced disruption of the blood-brain barrier promotes host death.
Developmental Cell.
Doi: https://doi.
org/10.
1016/j.
devcel.
2021.
08.
010[2] Can fruit fly research help improve survival.
Retrieved Sep.
17, 2021 from https://vcresearch.
berkeley.
edu/news/can-fruit-fly-research-help-improve-survival-cancer-patients