Here’s a term you don’t hear every day: hypoxic tumor. It describes a secret that explains a way used by prostate cancer (PCa) tumors to become more dangerous. The secret is called hypoxia, which literally means “low oxygen” (hypo = low, ox = oxygen).

Hypoxic tumors

We need oxygen for life. Respiration, or breathing, brings it into our lungs where circulating blood picks it up and distributes it throughout the body. Almost all cells in our body also have a form of “breathing” called cellular respiration by which they take in the oxygen they need to energize their proper functions.

This is just as true for PCa cells. As the tumor grows, the cancer cells hijack a healthy process called angiogenesis, which means building new blood vessels when needed. As an example, angiogenesis helps wounds heal by constructing extra blood vessels to energize busy repair cells. In the case of malignant cells, however, the blood vessels are chaotic. They don’t evenly distribute oxygen to the busy cancer cells. This means that some tumor cells are deprived of all the oxygen they need. They now have hypoxia. In fact, not just PCa, but all solid tumors are at risk of hypoxic areas.

When healthy cells are hypoxic, they are in trouble—and the same is true for PCa cells. But instead of dying off, tumor cells turn the tables. As described in “The Role of Hypoxia on Prostate Cancer Progression and Metastasis” (Mohamed et al., 2023), they activate biochemical signaling pathways to help them keep their self-renewal abilities, their strength, and their resistance to programmed cell death. Additionally, this surge of tumor defenses increases “the expression of androgen receptors on cancer cells maintaining the growth and survival of prostate cancer and the development of its castration resistance.”^[i] In other words, what PCa cells do in response to hypoxic conditions actually makes them more life-threatening, and with renewed growth the hypoxic areas also gain more volume.

A special type of MRI can help radiation patients

Unfortunately, we don’t yet have treatment approaches to block cancer from hijacking normal biologic pathways in order to overcome hypoxia. However, there are now clinical studies of a new type of MRI called oxygen-enhanced MRI (OE-MRI) to identify and track hypoxic activity. When a patient inhales oxygen at the start of a scan, his entire body becomes oxygen-enriched. During the scan, use of a specialized contrast agent highlights low-oxygen tumor areas. Here’s how this can benefit patients during many weeks of radiation treatments.

Many types of solid tumors are treated with radiation, which does not instantly destroy cancer but gradually disarms tumors by harming their cells so they slowly die off. But this is hard to track in real time, so a new imaging method was needed. A 2016 publication explains, “Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) techniques were evaluated as potential non-invasive predictive biomarkers of radiation response.”^[ii] The authors tested this by implanting lab rats with PCa tumors and treating them with hypofractionated radiotherapy. They note, “Radiation-induced hypoxia changes were confirmed using a double hypoxia marker assay. Inhaling oxygen during hypofractionated radiotherapy significantly improved radiation response.” Thus, with repeat OE-MRI during the course of radiation therapy over several weeks, the response shows up in the form of ongoing hypoxia volume reduction, a promising sign of tumor die-off. It has not yet been tested with PCa patients undergoing radiation, but a small (10 patient) PCa study says it’s feasible to integrate OE-MRI into multiparametric MRI (mpMRI) to gain “…further insights into the pathophysiological information of tumor microenvironment.”^[iii]

However, a 2024 journal article announces results of an OE-MRI/radiation clinical trial with human patients—in this case, oropharyngeal cancer (tumor in the rear of the mouth and neck).^[iv] The study enrolled 27 patients, of which 24 were eligible for analysis. All lesions were identified using OE-MRI at the start of radiation, then at 2 and 4 weeks during treatment. An Aug. 30, 2024 news story reports that

… hypoxic volume was reduced in 54.5% and 88.2% of individual lesions by weeks 2 and 4, respectively. Furthermore, all lesions with hypoxic reduction by week 2 saw sustained shrinkage through week 4, implying dose de-escalation may be performed for some patients before week 4 of radiation-based therapy.

That the radiation is working is good news for patients—and even more so the possibility of reducing the dose starting in the 4th week. The article goes on to quote principal clinical scientist Dr. Michael Dubec as saying, “Our aim is to destroy the tumor while preserving healthy tissue thus reducing toxicity. Using oxygen-enhanced magnetic resonance imaging to map hypoxia in patients’ tumors may improve the accuracy of their treatment.”

At the Sperling Prostate Center, we are optimistic that there will soon be clinical trials of OE-MRI with PCa patients undergoing radiation therapy. In our commitment to excellence in MRI-based prostate care, it’s easy to envision how broad implementation of OE-MRI will benefit patients everywhere.

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] Mohamed OAA, Tesen HS, Hany M, Sherif A et al. The role of hypoxia on prostate cancer progression and metastasis. Mol Biol Rep. 2023 Apr;50(4):3873-3884.
[ii] White DA, Zhang Z, Li L, Gerberich J, Stojadinovic S, Peschke P, Mason RP. Developing oxygen-enhanced magnetic
resonance imaging as a prognostic biomarker of radiation response. Cancer Lett. 2016 Sep 28;380(1):69-77.
[iii] Zhou H, Hallac RR, Yuan Q, Ding Y, Zhang Z, Xie XJ, Francis F, Roehrborn CG, Sims RD, Costa DN, Raj GV, Mason RP. Incorporating Oxygen-Enhanced MRI into Multi-Parametric Assessment of Human Prostate Cancer. Diagnostics
(Basel). 2017 Aug 24;7(3):48.
[iv] Dubec MJ, Price J, Berks M, et al. Oxygen-enhanced MRI detects incidence, onset and heterogeneity of radiation-
induced hypoxia modification in HPV-associated oropharyngeal cancer. Clin Cancer Res. Published online August 15, 2024. doi:10.1158/1078-0432.CCR-24-1170