Radiation therapy can be a successful treatment for prostate cancer (PCa). In some cases, though, a tumor can resist the effect of radiation and go on to spread (metastasize) to other places in the body. At that stage, the disease is considered incurable.

However, researchers are working on ways to counter such resistance. One such approach involves combining radiation with immunotherapy to mobilize the immune system. To understand how a combination could help, it’s important to learn how tumor cells develop radiation resistance.

How tumor cells become resistant

Tumors are made up of cancer cells, but other noncancerous cells and biochemicals are also present. Prostate cancer cells use these resources to fuel and defend their own activity and growth, so together they form what’s called the tumor microenvironment (TME). One TME component is myeloid cells.

Myeloid cells are everywhere in the body. They arise in bone marrow and circulate in the bloodstream, and they play an important role in the body’s immune system and healing tissue damage. As PCa tumor cells (and other normal cells) are damaged by radiation, myeloid cells are activated. They send biochemical signals to other cells in a process called adenosine signaling. Cancer “hijacks” this in a way that suppresses normal immune system defenses so the signaling cells are called myeloid-derived suppressor cells.^[i] Many tumor cells are then able to resist the effect of radiation. The surviving cells have the capacity to metastasize.

A new way to overcome resistance

One physician-scientist, Dr. Catherine Spina (Columbia University Irving Medical Center) has focused her research on a new possibility for overcoming resistance. The work of her and her colleagues is developing immunotherapeutic pharmaceuticals that can be paired with radiation during treatment.

They have recently launched a clinical trial to test SBRT (stereotactic body radiation therapy) in combination with two different types of immunotherapy pharmaceuticals:

• One drug to block adenosine signaling
• One drug to boost the immune system

Study participants will be men with metastatic PCa. All participants will receive the radiation treatment followed by immune drugs. They will be monitored for 6 months, with the primary endpoint being the effectiveness of the treatment protocol on disease progression. Secondary objectives include assessment of bRFS (no rise in PSA) survival at 6 months, with treatment response also being evaluated using CT imaging, nuclear bone scan, and PSMA-PET at 6 months. Records will be kept on safety and tolerability.^[ii]

Conclusion

Clearly, this is very important research given that there is no cure yet for metastatic prostate cancer. By delving into the tumor microenvironment to analyze how it promotes resistance to radiation, scientists like Dr. Spina hope to find a key to unlock one of the ways by which PCa tumors escape the effectiveness of radiation.

Then, developing a treatment to defeat such resistance holds the promise of an eventual cure. All of us as Sperling Prostate Center send our wishes for success to Dr. Spina and her team.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Barry, S.T., Gabrilovich, D.I., Sansom, O.J. et al. Therapeutic targeting of tumour myeloid cells. Nat Rev Cancer 23, 216–237 (2023).
[ii] Patel, M et al. Trial in Progress: A Phase II Single-Arm Study Testing SBRT, Adenosine Signaling Modulation, and Immune Checkpoint Inhibition for Men with Hormone Sensitive Oligometastatic Prostate Cancer (SBRT-AMICO). Intl J Rad Onc, Biol, Phys. 2025 Sep:123(1) Supplement e592