Recent advancements in cancer treatment have prompted significant research into methods that enable targeted delivery of therapies to difficult-to-access tumors, particularly those located in the brain. A preclinical study conducted by investigators at Cedars-Sinai Medical Center has revealed the potential of a unique protein designed to cross the protective blood-brain barrier and deliver therapeutic agents directly into tumor cells, heralding a promising new approach in oncology.

The Challenge of Targeting Brain Tumors

The blood-brain barrier presents a formidable challenge for delivering chemotherapy to tumors that have metastasized to the brain. This barrier protects the brain from potentially harmful substances but also limits the access of therapeutic agents. Dr. Lali Medina-Kauwe, a leading researcher in the study, notes, “One of the most challenging tumors to treat is cancer that has spread to the brain,” emphasizing the need for innovative solutions to this pressing problem.

Mechanism of Action

In the study published in the journal Nature Nanotechnology, researchers demonstrated how their specially designed tumor-invading protein utilizes a receptor called HER3, which is present on both the blood-brain barrier and various cancer cells. The HER3 receptor facilitates the passage of the protein from the bloodstream into the brain, making targeted therapy feasible.

Experimental Methodology

The research team utilized a novel blood-brain barrier "organ chip," an innovative laboratory device that simulates the blood-brain barrier environment. This organ chip contains compartments with human brain cells, allowing researchers to observe real-time interactions between the designed protein and the barrier.

  • When the protein was introduced into the blood vessel portion of the chip, it successfully crossed and accumulated in the brain cells.
  • Blocking HER3 receptors inhibited the protein’s ability to traverse the barrier, indicating the essential role of HER3 in this process.

Potency and Selectivity

The findings suggest that the tumor-invading protein effectively targets HER3-positive tumors, reducing their growth while sparing healthy cells. This selectivity is crucial, as traditional cancer treatments often affect both cancerous and non-cancerous cells, leading to adverse side effects.

“Most cancer drugs enter healthy cells as well as cancerous cells, causing major side effects, but this tumor-invading protein selectively enters tumor cells and spares the healthy cells.” – Dr. Ravinder Abrol, co-author of the study

Potential Applications

Cancer Type HER3 Status Current Therapeutic Options
Breast Cancer HER3-positive Hormonal therapies and chemotherapy
Lung Cancer HER3-positive Targeted therapies and immunotherapy
Colorectal Cancer HER3-positive Chemotherapy, targeted therapies
Metastatic Melanoma HER3-positive Immunotherapy, targeted therapies

Innovative Drug Delivery Strategy

Further enhancing the efficacy of this tumor-invading protein, researchers noted that its unique structure enables it to evade the cellular defenses that typically digest invading particles. Medina-Kauwe explained, “Most cells encapsulate invading particles in a bubble that allows the cell to harmlessly digest them. Our tumor-invading protein includes a pinwheel-like structure that prevents digestion.” This characteristic allows the protein to deliver a potent combination of therapies, including chemotherapy, directly to the tumor cells.

Future Directions

The study's promising results pave the way for future exploration into developing therapies capable of delivering treatments directly to advanced tumors with clinical implications. The researchers are particularly eager to investigate the delivery capabilities of the tumor-invading protein on various HER3-positive tumors:

  • Breast tumors
  • Lung tumors
  • Colorectal tumors
  • Primary brain tumors

Conclusion

The ability to deliver targeted therapies directly to brain tumors while minimizing harm to healthy tissues represents a significant step forward in cancer treatment. As Dr. Medina-Kauwe stated, these findings are a "major step toward developing therapies with reduced toxicity and enhanced safety profiles."

For more information on this study, refer to the full article: Lab study shows tumor-invading protein delivers therapy straight to the brain.

References

Alonso-Valenteen, F., et al. (2025). Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth. Nature Nanotechnology.

Cedars-Sinai Medical Center. (2025). Tumor-invading protein study details. Retrieved from Phys.org.