Commentary
Article
Beyond Earth: The Future of Cancer Clinical Trials in Space
Author(s):
Microgravity provides researchers with a unique environment for studying how cells behave differently than they do on Earth.
Space, the final frontier, is a vast expanse that is home to an estimated 200 billion galaxies, each teeming with an average of 100 million stars.1 With its infinite possibilities, this enormity of the cosmos has always captivated the human imagination. As we continue to explore the depths of the universe, experts are beginning to ask whether we can harness its unique conditions to confront one of the most complex and persistent challenges we face on Earth: Cancer.
Cancer claims a staggering 10 million lives each year.2 Despite significant advancements in the field, the path to a cure remains arduous. To comprehend the potential of space in addressing this challenge, we must first understand current treatment paradigms and what they lack.
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Current Treatments & Challenges
Current treatment paradigms for cancer include immunotherapies, cell therapies, chemotherapies, and gene therapies. Although these approaches have made huge leaps forward over recent decades, they still present significant challenges and concerns.
For instance, immunotherapy, which boosts the body's immune system to fight cancer, can inadvertently lead to the immune system attacking normal organs and tissues, causing severe side effects. Cell therapy, which involves infusing living cells into a patient, can result in high fever, breathing difficulties, and low blood pressure. Chemotherapy, while effective, can be extremely toxic to healthy cells. Gene therapy, which involves editing and delivering genes to the correct cells, carries the risk of unknown long-term impacts due to permanent changes in patients’ DNA.3
Moreover, these treatments may not be effective against all types of cancers. Given these challenges, the unique microgravity conditions in space offer a promising avenue for improving our understanding of cancer and developing more effective treatments.
Microgravity & Cell Behavior
Microgravity is a condition in which things seem to be weightless, like floating in space. It happens when objects, like rockets, fall toward a planet, but they move so fast sideways that they miss the planet and continue falling around it instead. This continuous falling creates a feeling of weightlessness for everything inside the spaceship, including astronauts and objects. That's how they experience "zero gravity" or "microgravity" in space.
The condition of near weightlessness experienced in space provides researchers with a unique environment for studying how cells behave differently than they do on Earth. It affects various aspects of cell behavior, such as their growth, gene activity, and how they respond to signals. When it comes to cancer cells, researchers have discovered that microgravity can accelerate their growth, change how they go through their life cycles, and make them more resistant to cell death.4 These findings are valuable because they give experts new insights into cancer behavior, helping to develop better treatments and improve the fight against this disease.
Oncology Clinical Trials in Space
One such research project is leveraging microgravity to accelerate the regenerative capabilities of cancer cells, enabling the effect of novel treatments to be captured in a much shorter time than on Earth. In the weightlessness of space, cancer stem cells exhibit accelerated growth, their size tripling three-fold in just 10 days due to the activation of an enzyme called adenosine deaminase associated with RNA1 (ADAR1). ADAR1 enables cancer cells to replicate rapidly and elude the vigilant immune system.4
Building on this phenomenon, the Sanford Stem Cell Institute, in collaboration with the University of California, San Diego and the International Space Station (ISS) National Laboratory, has initiated a unique project to study cancer stem cells in microgravity. The research team is studying various types of tumor cells to understand if ADAR1 is activated as a stress response to microgravity and exploring therapies that can inhibit the activity of ADAR1.4,5
Similarly, the Institute of Cancer Research, London, in partnership with the UK space sector, is pioneering research aboard the ISS that centers on the growth of cancer cells in three dimensions.6 On Earth, the force of gravity confines cell growth primarily to 2-dimensional planes. However, in the microgravity environment of space, cancer cells manifest into 3-dimensional structures known as "tumor spheroids" or "organoids." These 3-dimensional models faithfully mimic their natural growth within the human body, affording scientists an unprecedented platform to study cancer cell interactions, development, dissemination, and response to various treatment modalities.6
The Frederick National Lab for Cancer Research has embarked on a study aboard the ISS to elucidate the structure of the KRAS protein, which is implicated in various cancers. Approximately 30% of human cancers carry mutations in the KRAS gene, making it a prominent target for cancer therapies.7 However, the protein's inherent flexibility presents challenges to study on Earth. In the microgravity environment of space, the protein can be crystallized, providing researchers with an opportunity to probe its structure in exquisite detail. This profound understanding of KRAS may herald the emergence of more effective treatments against cancer.7
Challenges & Limitations
Although conducting cancer research in the microgravity environment of space offers unique opportunities, it also presents significant challenges. The logistics involved in these experiments are complex, requiring extensive planning, coordination, and substantial financial resources. Sending samples to and from the ISS is not only time-consuming and incredibly expensive, but also requires meticulous handling to maintain sample integrity.
Additionally, the microgravity environment introduces variables that are not present on Earth, adding complexity to the interpretation of trial results. For instance, radiation exposure on the ISS is significantly higher than on Earth, a factor that must be considered when analyzing experimental outcomes. Moreover, physiological changes in astronauts due to long-term exposure to microgravity, such as immune system dysregulation and cardiovascular deconditioning, could influence the results. The limited resources and the constraints of conducting trials within the confined space of the ISS also pose challenges.
Potential Solutions
Overcoming the challenges of space-based cancer research requires innovative solutions. Advancements in robotics and automation can streamline the process of transporting samples to and from the ISS, ensuring their integrity. Advanced shielding technologies have the potential to mitigate the effects of increased radiation exposure on the ISS, providing a more controlled environment for trials. Telemedicine and remote monitoring technologies can help manage physiological changes in astronauts due to long-term exposure to microgravity, ensuring the accuracy of trial results. Lastly, partnerships with private space companies can provide additional resources and capabilities, helping overcome the constraints of conducting trials within the confined space of the ISS.
The cosmos, with its unique microgravity conditions, is not just a frontier for exploration but a promising laboratory for cancer research. Current space-based cancer research, while still in its nascent stages, is already yielding valuable insights into cancer cell behavior and potential therapeutic targets. Despite the logistical and environmental challenges, innovative solutions such as advanced robotics, shielding technologies, telemedicine, and strategic partnerships hold the potential to pave the way for more comprehensive and efficient space-based clinical trials. Our odyssey into the depths of space is not just about touching the stars, but about bringing rays of hope to millions affected by cancer here on Earth.
About the Author
Deepika Khedekar, MPharm, is a Clinical Trial Lead at IQVIA Inc, a global clinical research organization where she spearheads clinical trial monitoring programs for major pharmaceutical companies. In her more than 12 years in the pharmaceutical industry, she led phase 1, 2, and 3 clinical trial programs in the respiratory and gastrointestinal therapeutics and drugs for leading US and Australia-based pharmaceutical organizations, such as Gilead Sciences, Macleods Pharma, Arrowhead Pharmaceuticals, NoNO Inc., EpimAb, and Impact Pharma. She started her journey in the field of pharmaceutical research at Pfizer and holds a master’s degree in pharmacy from the University of Mumbai.
References
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2. World Health Organization. Cancer. February 3, 2022. Accessed August 9, 2023. https://www.who.int/news-room/fact-sheets/detail/cancer
3. Debela DT, Muzazu SGY, Heraro KD, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021;9. doi:10.1177/20503121211034366
4. ISS National Laboratory. Sanford Stem Cell Institute to Study Cancer Stem Cell Targeted Therapy in Space. May 11, 2023. Accessed August 9, 2023. https://www.issnationallab.org/ax2-sanford-stem-cells/
5. Mlynaryk N. UC San Diego First to Test Cancer Drugs in Space Using Private Astronaut Mission. UC San Diego Health. May 22, 2023. Accessed August 9, 2023. https://health.ucsd.edu/news/press-releases/2023-05-22-uc-san-diego-first-to-test-cancer-drugs-in-space-using-private-astronaut-mission/
6. Cancer cells set to be launched into space for microgravity experiment on the International Space Station. News release. The Institute for Cancer Research. March 24, 2023. Accessed August 9, 2023. https://www.icr.ac.uk/news-archive/cancer-cells-set-to-be-launched-into-space-for-microgravity-experiment-on-the-international-space-station
7. Smith AW. Space Crystals and the Search for a Cancer Cure: Using Microgravity to Improve Protein Crystallization. ISS National Laboratory. February 27, 2023. Accessed August 9, 2023. https://www.issnationallab.org/upward-kras-gene-frederick-national-lab/
