It's not you--it's cancer: CSHL Associate Professor Tobias Janowitz and colleagues discover the brain-body connection underlying apathy in cancer cachexia

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~ A recent study published in Science has shed light on the debilitating effects of cancer cachexia, a condition that affects both the body and mind of cancer patients. The research, led by Cold Spring Harbor Laboratory (CSHL) Associate Professor Tobias Janowitz and WashU Medicine Professor Adam Kepecs, reveals a brain circuit that is responsible for the apathy and lack of motivation often seen in patients with this condition.

According to Janowitz, who is also a co-team lead for CANCAN, a research initiative tackling the cachexia challenge set by Cancer Grand Challenges in 2020, many cancer patients experience symptoms of apathy and disinterest. "They say, 'I don't know what's going on with me. My relatives cooked my favorite meal. I don't feel like eating it.' Their grandchildren come for a playdate. Usually, they'd be excited and enjoy it. They just don't seem to engage so much," he explains.

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Aside from the emotional toll it takes on patients and their loved ones, cachexia also severely limits their ability to tolerate common cancer treatments. This has been an area of study for CSHL scientists for years, but this latest research marks a major breakthrough in understanding the underlying mechanisms behind cachexia-related apathy.

Janowitz and Kepecs discovered that as cachexia progresses, certain neurons release less dopamine - the brain's "feel-good" chemical. Through screening for elevated immune system proteins in mice with cachexia, they identified IL-6 as a key player in this process. IL-6 is released during inflammation and has long been associated with cachexia.

By decreasing IL-6 signals in connected brain areas, the researchers were able to increase motivation levels in mice with cachexia. This was evident when the mice became less sensitive to the effort required to find food. Similarly, elevating dopamine levels in specific brain areas also had the same effect.

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"This reveals that apathy isn't just an emotional or psychological reaction to cachexia - it's built into the biology of the disease," says Kepecs.

The discovery also suggests that existing antibody treatments could potentially be repurposed to improve the quality of life for cancer patients. As Janowitz explains, "Our goals are to make patients feel better and to treat the cancer better. A better patient will be able to better tolerate and benefit from anti-cancer treatments."

The researchers credit their interdisciplinary approach, combining cancer and neuroscience research, for this significant finding. They hope that through continued collaboration, they can ultimately help turn cachexia into a condition that patients can overcome. This would not only benefit those battling cancer but also their loved ones who suffer alongside them.

In conclusion, this new research sheds light on the biological basis of apathy in cancer cachexia and offers potential avenues for improving patients' quality of life. With further studies and collaboration, there is hope for a future where cachexia is no longer a debilitating condition for cancer patients.
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