Pleural mesothelioma is a rare cancer that develops in the lining of the lungs and is caused by asbestos. Because it takes 10-50 years for mesothelioma to develop after exposure to asbestos, the cancer isn’t diagnosed until it is in later stages, making it harder to treat in many cases.

A collaborative study by several institutions in Japan examined a new approach to mesothelioma treatment. These researchers sought to test the effectiveness of two experimental drugs that suppress cancer cell growth by targeting specific enzymes and proteins.

The treatment combination slowed cancer tumor growth better than each drug alone.

By exploring this treatment, researchers can find effective combinations that can potentially lead to better outcomes for mesothelioma patients. Learn more about the study results below.

Combining Targeted Therapy Drugs for Maximum Effect

In this recent study published in Molecular Cancer Therapeutics, researchers tested two targeted therapy drugs. These types of medications work on specific proteins in cancer cells to disrupt the cell growth process.

  • AZD6738, a protein inhibitor that decreases the activity of an enzyme called ATR, which allows cancer cells to replicate and repair themselves when damaged
  • ONO7475, a drug that targets a receptor protein called AXL, which influences replication, mobility (movement), survival, and drug resistance in cancer cells

By combining these two mesothelioma drugs, mesothelioma specialists believed they could potentially slow down tumor growth.

The best mesothelioma doctors are constantly testing new treatment combinations like this one to help people with mesothelioma live longer. Find a doctor near you so you can improve your chances of survival with our Free Doctor Match program.

AZD6738, ATR, and Mesothelioma: The 2-Part Study

This study tested the response of inhibitors targeting ATR and AXL proteins on different types of mesothelioma cells and in mice with mesothelioma tumors.

The study was conducted in two parts:

  1. Doctors examined the response of ATR and AXL inhibitors on 14 pleural mesothelioma tumor samples representing the three cell types of this cancer: epithelial, sarcomatoid, and biphasic.
  2. The most viable tumor samples were injected into mice to explore how the cancer would respond to treatment.

This approach allowed researchers to gather data on how the drugs worked when combined as well as when administered separately.

Key Takeaways From Part 1

The analysis of the 14 mesothelioma cell samples showed that combining ATR and AXL inhibitors had a synergistic effect, meaning they worked well to maximize the effects of one another.

When the AXL pathway was suppressed, the ATR inhibitor was more effective at damaging cancer cells before they could repair themselves.

This combined treatment decreased:

  • Cell viability (ability of the cells to survive)
  • Cell motility (ability of the cells to move)
  • Overall tumor growth
  • The spread of cancer to healthy tissue

In 9 out of the 14 mesothelioma cell samples, combining the ATR and AXL inhibitors led to reduced viability of tumor cells. These results show great promise for the combination treatment.

Results of Part 2

In part 2, researchers took the epithelioid mesothelioma cell sample from the first part of the study and injected it into mice to test the model.

Once the tumors grew to a certain point, the mice were divided into 3 groups, with:

  • 1 group receiving AZD6738
  • 1 group receiving ONO7475
  • 1 group getting both AZD6738 and ONO7475

The mice tolerated both the individual inhibitors and the combination therapy well, as there was no severe loss of body weight observed.

Part 2 of the study confirmed the effectiveness of combining ATR and AXL inhibitors in reducing tumor growth in mice with epithelial mesothelioma.

Researchers were optimistic about the results and feel that the use of ATR and AXL inhibitors may be a promising therapeutic strategy to slow mesothelioma progression and improve patient outcomes.

Find New Treatments From a Mesothelioma Specialist Near You

Advancements in mesothelioma treatment are being made every day and some patients are living for years or even decades. Receiving treatment from experienced mesothelioma specialists is the best way to access targeted therapy and other emerging treatments.

If you or someone you love has been diagnosed with mesothelioma, we are here to help you access personalized medical treatment, financial compensation, and other support.

Connect with a Patient Advocate now at (866) 608-8933 or get started with our Free Doctor Match.

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Laura WrightWritten by:

Lead Editor

Laura Wright is a journalist and content strategist with more than 15 years of professional experience. She attended college at the University of Florida, graduating magna cum laude with a bachelor’s degree in journalism in 2008. Her writing has been featured in The Gainesville Sun and other regional publications throughout Florida.

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References
  1. Hirai, S., Yamada, T., Katayama, Y., et al. (February 2024). Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells. Molecular Cancer Therapeutics. Retrieved March 14, 2024, from https://aacrjournals.org/mct/article/23/2/212/733945/Effects-of-Combined-Therapeutic-Targeting-of-AXL

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