In a new study from the University of Chicago, researchers found that low doses of a four-drug combination may help prevent the spread of cancer without triggering drug resistance or recurrence.
The findings suggest a new approach to preventing cancer metastasis in patients by simultaneously targeting multiple pathways within a metastasis-promoting network.
They may also help identify people who would most likely benefit from such treatment.
Metastasis, the spread of cancerous cells through the body, is a common cause of cancer-related deaths.
Current approaches to treating metastatic cancer have focused on high doses of individual drugs or drug combinations to hinder pathways that promote the spread of cancer cells.
But these approaches can be toxic to the patient, and may inadvertently activate other pathways that cause the drugs to stop working and the tumors to return.
In the study, the team analyzed gene data from patients to understand how a metastasis-suppressing protein called RKIP works.
They found that RKIP reduces the expression of a network of genes that promote the spread of cancer cells.
The team then created a four-drug combination that mimics how RKIP suppresses the ability of cancer cells to spread.
They administered low doses of this treatment to mice with metastatic cancer that mimics metastatic breast cancer, and found that it blocked the spread of cancer and increased the animals’ survival.
Importantly, the treatment did not trigger the compensatory mechanisms that often cause high-dose, anti-metastasis drugs to stop working and tumors to return.
Finally, the team used computer modeling to explain why reducing, but not completely stopping, the expression of this network of genes helped prevent metastasis without triggering drug resistance or relapse.
They also identified patients with breast cancer who might be most likely to benefit from such treatment based on their cancer’s gene expression patterns.
These findings could lead to a new cancer treatment strategy where patients first receive low-dose combination drugs that block metastasis and then receive traditional cancer treatments such as radiation, chemotherapy or immunotherapy.
The results challenge current approaches to cancer treatment and suggest an alternative strategy for controlling metastasis in breast cancer and potentially other types of cancer
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The study is published in eLife. One author of the study is Ali Yesilkanal.
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