Did you know that normal oxygen levels inside and surrounding the tumors are critical for effective cancer treatment?
Studies have found that when a tumor stays in a low oxygen status called hypoxia, it becomes resistant to many treatments. These treatments include radiation, chemotherapy, targeted therapy, and immunotherapy. The hypoxia also promotes tumor progression, a dangerous condition for cancer patients.
Two Approaches to Reverse the Hypoxia Condition in Tumors
Through continued research partially funded by the National Foundation for Cancer Research (NFCR), scientists have revealed the leading cause of hypoxia. Hypoxia happens because of the formation of defective blood vessels in tumor tissues. To repair the defected blood vessels and reverse the hypoxia condition, a research team led by NFCR-funded scientist Dr. Rakesh K. Jain, Director of the Steele Laboratories for Tumor Biology at Massachusetts General Hospital, has developed two approaches. The first one is to inhibit a cellular signaling system called Vascular Endothelial Growth Factor (VEGF) Pathway in tumor cells. This method could transiently improve blood flow and oxygenation in tumors. The other approach utilizes angiotensin receptor blockers, such as the high blood pressure drug Losartan to alleviate the blood vessel collapse caused by growing tumor mass.
Reduced Hypoxia Could Improve Certain Cancer’s Survival Rate
Research data shows that both approaches hold the promise to reduce tumor hypoxia by improving oxygenation in tumors. Additionally, these methods increase blood flow, improving the delivery of anticancer drugs or cancer-killing immune cells to the tumor sites. A clinical trial also showed that the combination of Losartan with radiation and chemotherapy significantly improved survival rates for pancreatic cancer.
Understanding the Dynamics of Hypoxia is Critical for Treatment
However, Dr. Jain’s team found that the two approaches don’t always produce the same effects on patients with different diseases. Through further research, Dr. Jain’s team revealed that the tumor hypoxia doesn’t stay at one level all the time. The hypoxia levels vary in different tumor locations and times. As such, the hypoxia-reversion approaches won’t achieve their potential therapeutic effects without a clear understanding of the spatial and temporal heterogeneity of tumor hypoxia.
Research Innovation Will Improve Patients’ Treatment Outcomes
Constant innovation is always the main driving force in research. To measure the temporal and spatial changes in oxygen in tumors, Dr. Jain’s team developed a unique microscopy system and a special low-molecular-weight agent called palladium porphyrin probe. This research system enables the researchers to understand the dynamic changes in oxygen level and hypoxia condition after applying Losartan and VEGF pathway inhibitors.
Dr. Jain’s research results were published in the journal of Clinical Cancer Research on May 18, 2022. More data will be collected and analyzed while the project continues. Future data will provide insightful information to help doctors optimize the dose and schedule of Losartan and other medications. With improved oxygenation and reduced hypoxia condition in tumors, patients will have lower rates of drug resistance and improved therapeutic outcomes in the future.
- Multiphoton phosphorescence quenching microscopy reveals kinetics of tumor oxygenation during anti-angiogenesis and angiotensin signaling inhibition. Clinical Cancer Research, May 18, 2022.
- Novel protocol improves pancreatic cancer outcomes. The Harvard Gazette, May 30, 2019.