Imagine you’ve just been diagnosed with lung cancer. Only instead of prescribing a physically challenging course of radiation or chemotherapy, your oncologist hands you an inhaler with at-home treatment instructions, followed by office check-ups to monitor for changes in tumor progression.
Given the current reality of lung cancer, such a scene seems far-fetched. A lung cancer diagnosis presages months, if not years, of gruelling treatment that may include surgery, radiation, chemotherapy, targeted therapy or immunotherapy, typically in combination—many of which come with toxic side effects.
It is this dilemma that makes inhaled therapies for lung cancer so attractive. Fortunately, thanks to decades of development in the inhaled delivery of treatments for asthma and smoking-related diseases such as chronic bronchitis and emphysema, it has become a possibility worthy of serious consideration.
The pioneers of inhaled therapies simply took compounds meant to be delivered orally and aerosolized them for delivery to the lungs—but we now live in an era of “inhalation by design.” Concoctions of several therapeutics can be packaged in an easy-to-use, handheld device, and delivered at doses sufficient to have the desired effect yet low enough to prevent the drugs from escaping the lungs to negatively affect other sensitive organs.
These possibilities are only beginning to be explored for cancer therapeutics, however. Until recently, attempts were limited to compounds not originally designed for inhaled use, similar to the earliest days of other inhaled therapeutics. The tide shifted about a decade ago, when clinical trials of compounds designed for inhalation demonstrated moderate efficacy and a reduction of toxicity in non-targeted tissues. That allowed for an increase in the amount of compound that could safely be delivered to the lung, which ultimately resulted in a higher level of cancer cell death.
The field advanced further with the development of anti-sense oligonucleotides (ASO) and protein therapies, which are currently in development or clinical trials. These customized therapies are encapsulated in nanoparticles to ensure a stable vehicle to deliver chemotherapy to the lung. The first inhaled compounds and biologics for lung cancer using this strategy have entered clinical trials; Pieris and AstraZeneca recently announced a collaboration investigating the utility of anticalin proteins in lung diseases. While that project focuses on inflammation and immunological diseases, it could ultimately apply to oncology if the platform technology works.
Gene-editing tools also represent an opening for inhaled cancer therapies. With CRISPR and other gene modifications being used more in cystic fibrosis, it will be interesting to observe how and when oncology researchers attempt to overexpress a silent gene that prevents cancer, or silence a mutant gene driving cancer, and whether they will attempt to deliver it by inhalation.
Contract research organizations like Charles River Laboratories, where we work, have the expertise to redesign existing therapeutics or design new compounds optimised for inhaled delivery. This capability is complemented by formulation teams adept at delivering compounds with suitable properties to achieve maximum effect in the lung while fitting a practical number of doses in the appropriate delivery device.
Furthermore, when it comes to preclinical testing of inhaled therapies, the in vivo inhaled models developed for other respiratory illnesses can easily translate into the oncology setting. Using light-emitting cell lines and in vivo imaging techniques, cancer cells can be delivered and allowed to grow in the lungs of models. This potentially makes preclinical efficacy models of cancer treated with inhaled chemotherapeutic delivery a translatable platform that could support ongoing drug discovery efforts.
Could we use inhaled delivery to treat more people, more successfully and with better patient compliance? Is it unrealistic to envision a future where the typical lung cancer patient receives an inhaler to use regularly at home, thereby reducing hospital costs and improving the patient’s quality of life?
As the very popular 1970s TV program The Six Million Dollar Man once stated, “We have the technology.” Now, we can use it to rebuild our approach to one of the world’s most prevalent cancers.