This news release reports on preliminary research that suggested the CRISPR-Cas9 gene editing system might be capable of knocking out a gene that helps lung cancer tumors develop resistance to chemotherapy drugs. The was published in Molecular Therapy Oncolytics.
The news release mentions alternatives and doesn’t misrepresent the novelty of this approach, but it doesn’t address costs, give actual data on the observed results, or caution about the many hurdles of translating observations made in tissue samples and mice to human bodies. We also wish the headline hadn’t overreached.
Chemotherapy is a mainstay of treatment for advanced lung cancer, but its effectiveness is stunted because some tumors are either intrinsically resistant to it or develop resistance over time.
Eliminating such resistance could extend patients’ lives and reduce the doses of chemo needed to kill tumors, sparing patients from toxicity and leading to a better quality of life.
The news release mentioned this as a potential “affordable” way of making lung cancer treatment more effective, and that it can “hopefully help contain costs” and provide reliability that “increases the chance that insurance companies will provide coverage.”
However, it doesn’t mention the cost of either gene editing or chemo.
The release is unable to claim a benefit in humans since the study was done in cell cultures and mice models and findings in the lab don’t always translate to similar outcomes in humans.
But even in describing the benefits in animal models and cell culture, the release fell short. It says, “tumor growth stopped and there was a dramatic decrease in the volume of existing tumors when chemotherapy was combined with CRIPSP-Cas9, which was used to disable a tumor gene known as NRF2.”
But there’s no data to give readers a sense of the scope of this potential benefit, such as how much the volume decreased, for what period of time, and in what percentage of the tested samples.
The news release doesn’t talk about specific harms but it does note that “the CRISPR application being developed for lung cancer does not involve directly editing a patient’s genome — only the genes in the tumor.”
The release calls this application a “relatively conservative” use of CRISPR and that it might “provide a level of safety and reliability that is reassuring for patients.”
The release would have been better had it explained that there’s potential for viral vectors that are used to carry genes into the body to infect healthy cells as well as cancer cells; the study cites a need for “more effective delivery methods of these genetic tools to lung tissue” that would eliminate the potential for disrupting normal cells.
It would have been helpful to note why this is important: a germ line can be passed on to children while somatic mutations generally can not be passed on.
In the second paragraph the news release explains that this tumor shrinkage was observed “in both tissue culture and in a mouse.”
We think that should have come with a strong caution that results observed in tissue samples and mice are seldom sustained in human testing. For example, the researchers cite the lack of a safe and effective delivery system for these genetic tools into lung tissue (see harms). It would have been better to stress in the release that this study was a “proof of concept” which would need to be transitioned into human subjects.
The news release also doesn’t tell us much else about how these studies were performed — in how many mice and tissue samples, for example. According to the study, a reduction in tumor growth was observed in an immunocompromised mouse for 16 days.
There’s no disease-mongering. The release says lung cancer is “the leading cause of cancer death in the United States.”
The news release could have helped readers by explaining how many patients are in a position to possibly benefit — that is, how many patients have cancer that is resistant to chemotherapy drugs or how many develop resistance after being exposed to the drugs — as well as whether this would apply to non-small cell or small-cell lung cancer, or both.
The funders (NIH and State of Delaware) are noted on a sidebar on the EurekAlert! site which hosts the release. We encourage news release authors to include funding sources in the body of the release as well.
The authors did not report any conflicts of interest.
The news release mentions “many efforts under way to modify CRISPR so that it can be used to not only remove or ‘knock out’ a section DNA, but also to replace or ‘knock in’ a new strand of code.”
It’s also worth noting that there have been theories about “re-sensitizing” tumors to treatment that have not been successful, usually having to do with the sequence of drugs given after the first line.
The news release makes it clear that this is not yet a treatment option.
The lead researcher calls the study “an exciting step in the journey of exploring the health benefits of gene editing” and says it is focused on a technique of cutting out the resistance gene using CRISPR. This would be a novel approach and a novel use of CRISPR.
In the study, the authors say that to their knowledge, “we are the first to generate” cells that are deficient in a gene NRF2, which helps promotes chemotherapy resistance in lung tumors.
The news release uses cautious language. However, the headline overreaches in declaring that “CRISPR restores effectiveness of lung cancer treatment.”