A Breakthrough Milestone In Cancer Research And Treatment

The news of cancer diagnosis brings turmoil in the lives of the patient and their caregivers. Enormous doubts about access to the right treatment and life expectancy begin to gather in thoughts. Even post-treatment, one of the most common fears survivors have is that the cancer might come back.

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However, significant strides in cancer research bring a bright ray of hope for cancer patients with an anticipation for a better tomorrow. Recently, scientists and researchers associated with India’s premier institute, Tata Memorial Centre (TMC), have proposed to find a novel nutraceutical that may reduce the toxicity associated with cancer treatment and reduce its recurrence rate.

Let’s understand about the spread of cancer
Cancer cells possess a menacing property by which they can sometimes spread from their primary site to other parts of the body. This is referred to as ‘metastasis’. Metastasis poses a significant challenge in cancer care and treatment.

What is this research about?
Recent research by Tata Memorial Centre examined if cancer treatment modalities like chemotherapy, radiotherapy, or surgery, while effective in addressing the primary tumor, might produce dying cancer cells, which could inadvertently facilitate metastasis. [1]

Growing research suggests that these dying cancer cells release cell-free chromatin particles (cfChPs, or fragments of chromosomes) that readily enter healthy cells, turning them into cancerous ones. [2]
To study this, researchers from the Translational Research Laboratory, TMC, ACTREC(The Advanced Centre for Treatment, Research and Education in Cancer. [1]

1. Grafted human breast cancer cells in immune-deficient mice to generate tumors.
2. The mice then received treatment in the form of chemotherapy, radiotherapy, or surgery.
3. Half of them also received agents that deactivate or destroy cfChPs.

The study’s results found:
1. The presence of human DNA (cfChPs) and cancer proteins in the mice’s brains. Interestingly, these substantially increased after treatment, especially chemotherapy and radiotherapy.
2. Mice that had received agents to deactivate or destroy cfChPs had minimal human cfChPs or cancer proteins in their brains.

The findings made a strong case that:
1. cfChPs may contain cancer-causing genes that have the ability to circulate through the body and transform healthy cells into cancerous ones.
2. More importantly, administering cfChP-deactivating/destroying agents could potentially mitigate metastasis.

What are these agents that could potentially deactivate or destroy cfChPs? The Magic of R+Cu
It is a combination of the widely available nutraceuticals resveratrol (a natural compound found in red wine and grapes) and copper. Nutraceutical is any product derived from food sources with postulated health benefits.
Another study [3] also found that this pro-oxidant combination down-regulates toxicities in patients receiving high doses of melphalan, a chemotherapy drug for multiple myeloma.
It is proposed that this combination might work by:

1. Binding to cfChPs: Resveratrol and copper can potentially bind to cfChPs, preventing them from entering healthy cells.
2. Triggering cfChP degradation: This binding may also trigger the breakdown of cfChPs, rendering them harmless.

Implications for Cancer Treatment
These findings have significant implications for how we approach cancer treatment.

1. Consider the role of cfChPs in cancer propagation: cfChPs could be a potential cause of metastatic cancer spread rather than metastasis being caused by migrating cancer cells.
2. Target cfChPs: Deploying agents/drugs to deactivate or destroy cfChPs circulating in the bloodstream could help prevent their potential role in metastasis.
3. Combine treatment approaches: Combining conventional cancer treatments with cfChP-deactivating agents might be a more comprehensive approach to managing the disease.

Final Takeaway
Understanding the role of cfChPs in cancer metastasis is a significant step towards better management of a complex condition like cancer. While further research and human trials are needed to elucidate the mechanisms at play and develop optimized therapies, the knowledge of cfChPs and the potential of nutraceuticals in combating them offer great hope for a better future.

(The article is written by Dr. Nitika Makhija, Manager, Clinical Health and Content)

1. https://pib.gov.in/PressReleaseIframePage.aspx?PRID=2009169
2. Raghuram GV, Tripathy BK, Avadhani K, Shabrish S, Khare NK, Lopes R, Pal K, Mittra I. Cell-free chromatin particles released from dying cells inflict mitochondrial damage and ROS production in living cells. Cell Death Discov. 2024 Jan 15;10(1):30. doi: 10.1038/s41420-023-01728-z. PMID: 38225229; PMCID: PMC10789803. Available online: https://pubmed.ncbi.nlm.nih.gov/38225229/
3. Agarwal A, Khandelwal A, Pal K, Khare NK, Jadhav V, Gurjar M, Punatar S, Gokarn A, Bonda A, Nayak L, Kannan S, Gota V, Khattry N, Mittra I. A novel pro-oxidant combination of resveratrol and copper reduces transplant related toxicities in patients receiving high dose melphalan for multiple myeloma (RESCU 001). PLoS One. 2022 Feb 4;17(2):e0262212. doi: 10.1371/journal.pone.0262212. PMID: 35120140; PMCID: PMC8815866. Available online: https://pubmed.ncbi.nlm.nih.gov/35120140/

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