A recently published pioneering study has uncovered a new methodology of how to improve cancer therapies. Scientists have been using the CD36 protein to increase their potency. Duke University School of Medicine, the University of Texas Health Science Center at San Antonio, and the University of Arkansas performed a critical study. Their work appeared in the journal Cell, published on April 17th. This study confirms that the CD36 pathway significantly enhances the uptake of bulky cancer therapeutics. In turn, that creates opportunities to discover better, more effective treatments.
This research proves that by taking advantage of the CD36 protein, we can achieve a significant improvement in drug delivery directly to cancer cells while avoiding healthy cells. To achieve this additional potency increase, the researchers developed a new strategy termed chemical endocytic medicinal chemistry (CEMC). Public health campaigns made them between 8 and 23 times more effective than previous formulations!
Understanding the CD36 Pathway
The CD36 protein doesn’t just help fat enter cells, it acts as a kind of bouncer to allow in larger molecules, such as many cancer drugs. This study suggests that the CD36 pathway serves as a novel way to significantly increase the intracellular levels of large cancer therapeutics. As did we, and by as much as 22.3-fold! This finding is an exciting and crucial discovery because many conventional cancer treatments struggle to penetrate cell membranes.
The researchers focused their efforts on a new class of drugs known as PROTACs. These drugs are designed to precisely home in on and destroy individual proteins within cells. That study tested these PROTACs, and they go beyond 1,000 Da in molecular weight. This unusual size often makes it difficult to develop pharmaceuticals due to the “Rule of 5.” Yet compounds larger than ~500 Da fail to absorb well in biological systems. This rule underscores the major hurdle continued development must surmount to bioactivate these more complex, larger compounds.
Chemical Endocytic Medicinal Chemistry
The research team addressed these limitations directly. They utilized CEMC, an approach that takes advantage of the natural cellular process of endocytosis. Through the process of endocytosis, cells can internalize exogenous molecules, enabling their use and internal processing. By leveraging this process, the researchers were able to improve drug delivery accuracy by more than 80%.
Taken together, these results suggest that the optimized PROTACs retained advantageous stability and solubility characteristics during the treatment course. This strategy has already been extraordinarily successful, having made great strides just in the past couple years with approved targeted cancer treatments. It is particularly advantageous for delivery of large-sized compounds, such as bRo5 molecules, which have a history of delivery challenges.
Independent Reproduction of Results
The study’s findings demonstrate the promise of this novel approach. Several research teams outside of the original research team have independently replicated the research, proving its effectiveness. Guiding this impressive collaborative effort are authors Hui-Kuan Lin, Hong-yu Li, and Zhiqiang Qin. Their findings are robust and open up new avenues of research to improve cancer drug delivery.
The researchers are hopeful about what these findings might mean for cancer treatment moving forward. By overcoming barriers associated with large drug molecules, they believe that this approach could lead to more effective therapies for patients battling various types of cancer.