Post-cure worry: Dying cancer cells can induce cancer in healthy cells, finds study

Led by Prof Indraneel Mittra from the Translational Research Laboratory at the Tata Memorial Centre’s Advanced Centre for Treatment, Research and Education in Cancer, over the span of a decade, the research team explored this complex phenomenon, seeking answers to the potential contribution of conventional cancer treatments — chemotherapy, radiotherapy and surgery — to the metastatic spread of cancer.

The study revealed a concerning phenomenon: dying cancer cells release chromosome fragments containing genes that have the potential to induce cancer in healthy cells. These fragments exhibit a remarkable ability to traverse the bloodstream, infiltrating healthy cells in various organs and triggering the potential spread of cancer to distant sites within the body.

The team’s recent study, conducted in collaboration with Dr R A Badwe, Prof Emeritus at TMC, and other senior researchers, also identified an unique deactivating agent, a nutraceutical, discovered in Prof Mittra’s laboratory. This agent demonstrated promising capabilities in preventing the invasion of chromosome fragments into healthy cells, raising the possibility that its administration may impede the metastatic spread of cancer. Administering cfChP-deactivating/destroying agents appeared to prevent this invasion into healthy cells, potentially preventing metastasis.

Prof Mittra emphasised the gravity of the findings, stating, “A unique yet dangerous property that cancer cells possess is their ability to occasionally spread from the primary site to other sites in the body. This is known as ‘metastasis’ and can be challenging to treat. It can even prove fatal after successfully treating the primary tumour with chemotherapy, radiotherapy, or surgery.”

The researchers, under Prof Mittra’s guidance, conducted experiments involving grafting human breast cancer cells into immune-deficient mice to generate tumors. The mice underwent various treatments, including chemotherapy, radiotherapy, or surgery, with half of them also receiving agents designed to deactivate or destroy cfChPs. Subsequent analysis of the mice’s brains revealed a significant increase in human DNA (cfChPs) and cancer proteins, especially after chemotherapy and radiotherapy.

The study indicated that cfChPs, originating from dying human breast cancer cells, migrated to the brain. Mice treated with compounds to deactivate or destroy cfChPs exhibited minimal human cfChPs or cancer proteins in their brains. This strongly suggests that cfChPs, potentially containing cancer-causing genes, could migrate through the bloodstream and enter healthy cells in other organs, instigating the metastatic spread of cancer. Crucially, the administration of cfChP-deactivating or destroying agents appeared to prevent their invasion into healthy cells, offering a potential strategy to hinder metastatic spread.

While advancements in cancer treatment have led to many patients being cured, this study revealed a potential risk associated with current cancer treatment practices. Chemotherapy and radiotherapy, while effectively targeting primary tumour cells, inadvertently lead to the release of cfChPs from dying cells. These particles can infiltrate healthy cells elsewhere in the body through the bloodstream, potentially causing cancer in new locations.

Prof Mittra urged a reconsideration of cancer treatment policies in light of these findings. “These findings have some important implications for cancer treatment policies. Clinicians need to consider cfChPs as a potential cause of metastatic cancer spread (rather than metastasis being caused by migrating cancer cells), and cancer treatment protocols may need to include drugs/agents that deactivate/destroy cfChPs,” he said.

Collaborating with a nutraceutical company, Tata Memorial Centre aims to commercialise chromatin-degrading agents, expected for release in June or July. This development holds promise in mitigating treatment-related toxicity, as demonstrated in human trials across various cancers.

Dr Navin Khattry, TMC’s deputy director, highlighted reduced toxicity in post-bone marrow transplant patients using the resveratrol-copper combination, suggesting potential use as adjuncts to chemotherapy and advancing the landscape of cancer care. The team’s findings, published in esteemed journals, represent a significant stride in cancer research, offering hope for a shift from treating to curing cancer.