The study found that targeting IL-6 (a cytokine that acts as both a pro-inflammatory and anti-inflammatory molecule) or directly boosting dopamine could help cancer patients feel better, stay engaged, and better tolerate cancer treatments.
Published Jun 04, 2025 | 7:00 AM ⚊ Updated Jun 04, 2025 | 7:00 AM
Cancer. Representational Image. (Creative Commons)
Synopsis: A study has uncovered a crucial biological reason behind cancer cachexia, which not only weakens the body but also rewires the brain, robbing patients of motivation and joy.
If you have witnessed a loved one battle cancer, you have likely seen their spirit fade along with their physical decline. Even the most spirited individuals often seem to lose the will to engage with life in the final stages.
Now, a detailed study published in Science has uncovered a crucial biological reason behind the heartbreaking phenomenon of cancer cachexia (a wasting syndrome common in late-stage cancer), which not only weakens the body but also rewires the brain, robbing patients of motivation and joy.
“Many patients complain of symptoms in that category. They say, ‘I don’t know what’s going on with me. My relatives cooked my favourite meal. I don’t feel like eating it.’ They wouldn’t engage much during playdates with their grandchildren, which they used to be excited about and enjoyed,” explained Xiaoyue Aelita Zhu from the Department of Neuroscience, Washington University School of Medicine, the US, one of the researchers of the study.
Speaking to South First, renowned oncologists in India revealed that this study is particularly significant for India, where over 14 lakh new cancer cases are reported every year, and family plays a pivotal role in caregiving.
While the emotional and psychological burden on families is immense, understanding that their loved ones’ withdrawal is biological — not a loss of willpower — can change the way palliative care and emotional support are structured.
The study, conducted by researchers from Cold Spring Harbor Laboratory (CSHL) and Washington University School of Medicine (WashU Medicine), found that apathy and loss of motivation in cancer patients suffering from cachexia are driven by a specific brain circuit activated by inflammation — and not just emotional or psychological stress.
For the study, the researchers implanted mice with colon adenocarcinoma cells (C26) to stimulate cancer cachexia. They found physical changes in the mice which included weight loss, muscle wasting and decreased feeding. Specific motivational deficits (seen in effort-based tasks like patch foraging and progressive ratio tests).
They found that there were no major changes in general movement, reward sensitivity (pleasure from sugar water), or despair behaviours.
Some of the major observations were:
The study also tried a few interception methods, which showed positive results on the mice.
Meanwhile, the study identified a clear immune-to-brain pathway that connects cancer-induced inflammation to loss of motivation.
The study found that targeting IL-6 (a cytokine that acts as both a pro-inflammatory and anti-inflammatory molecule) or directly boosting dopamine could help cancer patients feel better, stay engaged, and better tolerate cancer treatments. During cachexia, specific neurons in the brain reduce their release of dopamine — the chemical responsible for feelings of reward and motivation.
This shift is triggered by heightened immune signals, particularly IL-6.
“We discovered a full brain circuit that senses inflammation in the bloodstream and sends signals that reduce motivation,” said Adam Kepecs, co-author of the study. “This reveals that apathy isn’t just an emotional or psychological reaction to cachexia — it’s built into the biology of the disease.”
In experiments on mice with cachexia, blocking IL-6 signals or boosting dopamine levels helped restore motivation — a finding that could eventually lead to new supportive therapies for cancer patients.
Significantly, the research hinted that existing antibody treatments, some of which are already used in India for conditions like rheumatoid arthritis, could be repurposed to help cancer patients combat apathy and engage better with life — and their ongoing treatments.
“Our goals are to make patients feel better and to treat the cancer better,” Janowitz explained. “A better patient will be able to better tolerate and benefit from anti-cancer treatments.”
In India, where many hospitals are rapidly expanding palliative and supportive oncology services, these findings could open doors to new protocols that could address not just the tumour but the quality of life of patients.
Institutions like the All India Institute of Medical Sciences (AIIMS), Tata Memorial Centre, and several private cancer institutes are already focusing on holistic care models — and insights like these could soon be part of that evolving approach.
With the cancer burden projected to rise in India over the next two decades, this discovery offers a new frontier of hope, both for patients and for their families who walk the difficult road alongside them.
Speaking to South First Dr Lohith Reddy, Head of Radio Oncology at HCG Cancer Hospital, said, “In India, we often witness emotions unravelling in our cancer patients along with the physical toll of cancer. It is more common in patients with stage 4 cancer, who might be in the final months of their lives. Families go the extra miles to prepare the person’s favourite meals, organise get-togethers with their loved ones, plan moments of joy, or travel, only to see their loved ones disengaged or unresponsive and emotionally distant.”
He agreed that, until now, this apathy was often dismissed as emotional exhaustion or depression and that this new research has revealed something profound.
Cancer cachexia, Dr Reddy explained, is a wasting syndrome seen in many advanced cancer patients, which triggers an inflammatory response that affects dopamine — a neurotransmitter produced in the brain — and alters circuits in the brain. As a result, there is a biological shutdown of motivation and joy.
Dr Reddy said, “This explains why even the most positive patients in our hospitals and clinics stop enjoying their life, conversations, or even the company of their grandchildren.”
This insight, Dr Reddy said, is a game changer in cancer care in India and would help doctors understand that apathy is a symptom that they have to — and could — intervene in.
Meanwhile, Dr Narayana Subramaniam, Director of Head and Neck Surgery and Oncology at Sparsh Hospitals in Bengaluru, told South First that cancer therapy goes beyond the removal of the tumour through surgery, radiation, or the administration of chemotherapy.
He said, “With improved survival due to cancer therapies, patients are now living longer than before, but they have long-lasting symptoms from the cancer or its treatment that adversely affect their quality of life.”
“Given the large clinical load in our country, not all hospitals can focus on supportive treatment or rehabilitation. Additionally, treatment for these symptoms within a hospital becomes expensive and time-consuming,” he said.
Dr Subramaniam added that there is immense potential for supportive cancer therapies — physical, psychological, and others — that can be delivered partly remotely and partly in person (phygital) with a focus on patient well-being and recovery.
(Edited by Muhammed Fazil.)
