Chemotherapy drugs are often a key component of cancer treatment, however a new study has found a common chemotherapeutic agent, paclitaxel, could activate a pro-metastasis gene. The findings – published in the journal, Proceedings of the National Academy of Sciences – may call into question the safety of using paclitaxel to treat ovarian, breast and lung cancers.
Previous research conducted in mouse models, as well as in patients diagnosed with breast cancer, identified an association between the chemotherapeutic drug and cancer metastasis. Using a rodent model and patient data, researchers from Ohio State University in Columbus sought to better understand the molecular mechanisms by which paclitaxel could encourage breast cancer to spread to the lungs.
In analyzing the breast cancer patient data, the researchers found that patients who were treated using chemotherapy overexpressed a gene known as Atf3. The gene codes for a transcription factor that has been identified in a number of different cancer cell types and is involved in cellular stress.
“This gene seems to do two things at once: essentially help distribute the ‘seeds’ (cancer cells) and fertilize the ‘soil’ (the lung),” said Dr. Tsonwin Hai, a professor of biological chemistry and pharmacology at Ohio State University in Columbus.
Hai and his colleagues believe that this overexpressed transcription factor helps to promote the tumor microenvironment at the site of the primary tumor, as well as increase inflammation and reduce cytotoxicity in the lungs, which supports tumor cell growth.
“What is surprising to us is the multitude of pro-cancer effects that paclitaxel has,” Hai told Medical News Today. “It not only enhances the escape of cancer cells from the primary tumor but also facilitates the preparation of distant sites (lung in our case) in such ways that when the cancer cells arrive, they can set up shop and grow.”
The research team admits that their findings cannot prove a causal link between treatment with paclitaxel and cancer metastasis. In addition, their research focused on cancer spread through the blood as opposed the lymphatic system, which is another common route of cancer metastasis.
“Therefore, at this point, we are not suggesting oncologists to change their clinical practices but would suggest that it is prudent to keep our mind open, realizing that chemotherapy can be a double-edged sword,” said Hai. “It’s possible there could be a treatment given in conjunction with the chemo that would inhibit this problem by dampening the effect of the stress gene Atf3.”