Chemotherapy May Make Cancer More Likely to Spread

While chemotherapy is often the first treatment option for patients with cancer, a new study suggests that it may have unintended — and potentially lethal — side effects.

In a study using mouse models, researchers discovered that administering chemotherapy led to elevated levels of proteins and other markers that are tied to metastasis, or the spread of cancer throughout the body.

In other words, chemotherapy may lead to an increased risk of cancer spreading to other parts of the body, which is the leading cause of fatality among cancer patients.

The changes appear to occur on a cellular level, note the researchers from the Albert Einstein College of Medicine in New York City. That is, they found that chemotherapy administration led to a greater number of sites known as a tumor microenvironment of metastasis, or TMEM.

A TMEM occurs “when three specific cells are in direct contact,” note the researchers, and the more TMEM sites found within a tumor, the greater the risk that the cancer is going to spread.

For the study, the researchers treated the mice with breast cancer with a chemotherapy agent known as paclitaxel. After studying the effects of the treatment, the researchers discovered that the mice that had received paclitaxel had higher TMEM activity in their tumors.

“In addition, TMEM scores for mice that had undergone chemotherapy were two-to-three-fold higher compared with TMEM scores of mice not receiving chemotherapy,” report the study authors.

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When the researchers studied other chemotherapy agents, they found the same results. Also, when the researchers pivoted to human subjects, which included taking a biopsy specimen from 20 women with breast cancer who had received treatment with paclitaxel and other agents, the same effect occurred — the biopsy showed elevated TMEM levels, with five of the patients having more than a five-fold increase.

However, the insight gained on the mechanisms behind metastasis may lead to more effective treatment options. When the researchers administered the drug rebastinib, which is known to inhibit TMEM activity, the incidence of metastasis also slowed down.

The new study may encourage more careful monitoring of patients during chemotherapy administration, notes study author Dr. George Karagiannis of the Albert Einstein College of Medicine.

“One approach would be to obtain a small amount of tumor tissue after a few doses of preoperative chemotherapy,” said Karagiannis.

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“If we observe that the markers scores are increased we would recommend discontinuing chemo and having surgery first, followed by post-operative chemo. We are currently planning more extensive trials to address the issue,” he added.

The team of researchers plans to expand their trials to understand more types of disease.

“In this study we only investigated chemotherapy-induced cancer cell dissemination in breast cancer. We are currently working on other types of cancer to see if similar effects are elicited,” said Karagiannis.

The researchers note that the current study “provides insights into the mechanisms of chemotherapy induced cancer cell dissemination, potential targeted therapies to block chemotherapy-induced cancer cell dissemination and potential predictive markers to determine who may or may not benefit from pre-operative chemotherapy.”

The study appeared in the journal Science Translational Medicine.