There’s a molecule your body already makes that researchers across some of the world’s most respected institutions, NIH, Harvard, AACR, have spent decades studying in the context of cancer. It’s nitric oxide (NO). And the science around it is neither simple nor settled. But it is serious. This article is a clear, honest look at what the research actually says about nitric oxide and cancer treatment. No overclaiming. No cherry-picking. Just the science, explained in plain language.
The global cancer burden has reached a point that’s hard to overstate. According to the World Health Organization’s International Agency for Research on Cancer (IARC), there were an estimated 20 million new cancer cases and 9.7 million cancer deaths globally in 2022. About 1 in 5 people will develop cancer in their lifetime. [Source: WHO / IARC] In the United States alone, the National Cancer Institute (NCI) projects 2,041,910 new cancer diagnoses and 618,120 deaths from cancer in 2025. [Source: NCI] These numbers explain why researchers keep looking beyond standard treatments. Chemotherapy, radiation, and surgery remain the backbone of cancer care, but drug resistance, metastasis, and treatment side effects continue to limit outcomes for millions of patients. That’s precisely why nitric oxide has attracted so much scientific attention.
Nitric oxide is a gaseous molecule the body produces naturally from the amino acid Larginine. It’s made through a family of enzymes called nitric oxide synthases (NOS), which come in three forms:
eNOS (endothelial NOS) – found in blood vessel walls, regulates vascular tone and blood pressure
nNOS (neuronal NOS) – found in nerve cells, involved in brain signaling
iNOS (inducible NOS) – activated during inflammation and immune responses, capable of producing high concentrations of NO
Each isoform matters in cancer biology, and they don’t all behave the same way. That nuance is central to understanding this entire field. As a 2025 review published in Molecules (MDPI) and indexed in PMC/NIH put it, NO “exerts both protective and cytotoxic effects depending on its local concentration,” synthesized from L-arginine by NOS, it plays a pivotal role in cardiovascular regulation, immune response, and neurotransmission. [Source: PMC/NIH — Myśliwiec et al., Molecules 2025] That phrase, “depending on its local concentration,” is the most important thing to understand about nitric oxide and cancer. Low concentrations and high concentrations don’t just differ in degree. They can produce opposite effects.
This is where most popular coverage of nitric oxide gets it wrong. People either frame it as a cancer-fighter or a cancer-promoter. The actual science says it’s both, depending on where it is, how much of it is present, and what kind of tumor is involved.
When iNOS is chronically active at low-to-moderate levels in a tumor, the NO it produces can actually help the tumor thrive. Low-level NO promotes angiogenesis, the formation of new blood vessels that feed the tumor. It can also trigger anti-apoptotic signaling, meaning it helps cancer cells avoid the programmed death that would otherwise stop their growth. Research published in ScienceDirect has confirmed that iNOS overexpression in tumors increases angiogenesis, and that higher expression of iNOS in breast cancer has been associated with poor clinical outcomes. [Source: ScienceDirect] A 2019 systematic review and meta-analysis published in BioMed Research International (Wiley / Hindawi); covering 14 studies and 1,758 cancer patients, found that increased iNOS expression was significantly associated with worse overall survival in gastric, bladder, and colorectal cancers. [Source: BioMed Research International / PMC] That’s a concerning finding, and an honest one. It shows why researchers can’t simply say “more NO = better outcomes.”
Flip the concentration and the picture changes completely. When NO reaches high concentrations in tumor tissue, it becomes toxic to cancer cells. It activates p53; one of the body’s primary tumor suppressor proteins, triggering a cascade that leads to apoptosis (programmed cell death). Research published in Cancer Research (American Association for Cancer Research) confirmed that NO-induced apoptosis is substantially dependent on p53 activation. Treatment with NO donors induced DNA fragmentation, nuclear condensation, cytochrome c release, all markers of apoptotic cell death, with p53 required for at least 50% of NO-induced apoptotic cell death in human lymphoblastoid cells. [Source: AACR / Cancer Research]
This is why the scientific and clinical interest in NO-based cancer therapy is focused not just on increasing NO, but on delivering it in high concentrations to the right place, the tumor, without flooding the rest of the body.
To understand why NO research matters for cancer treatment, you need to understand the tumor microenvironment (TME), the ecosystem surrounding and supporting a tumor. The TME includes blood vessels, immune cells, signaling proteins, and chemical gradients. Tumors are skilled at manipulating this environment to survive. One of the ways they do it is by exploiting NO signaling. A landmark 2023 review published in Clinical Cancer Research (the journal of the American Association for Cancer Research), authored by researchers from Houston Methodist, the University of Pittsburgh, and the NIH, concluded: “Targeting nitric oxide synthase (NOS), a protein within the tumor microenvironment, has gained interest as a promising therapeutic strategy to reduce metastatic capacity and augment the efficacy of chemo/radiotherapies in various solid malignancies.” [Source: AACR / Clinical Cancer Research, May 2023] The same review noted that in lung adenocarcinoma patients, tumors with high expression of iNOS were associated with lower overall survival compared to those with low iNOS expression, reinforcing the complexity of this relationship and the importance of precision in how any NO-based strategy is applied.
Multidrug resistance (MDR) is one of the main reasons cancer treatments stop working over time. Cancer cells develop the ability to pump chemotherapy drugs back out before they can cause damage, largely through proteins called ABC transporters (such as Pglycoprotein, or P-gp). This is where some of the most compelling NO research lives.
A 2021 study by the National Cancer Institute (NIH, published in Cancers, MDPI), led by researchers at the NCI’s National Institute of Environmental Health Sciences, found that nitric oxide, specifically from an NO donor compound called NCX-4040, inhibited the ATPase function of ABC transporters, causing reversal of resistance to both Adriamycin and topotecan in multidrug-resistant human cancer cell lines. The study also found that NO significantly enhanced drug accumulation inside MDR tumor cells. The authors concluded: “Tumor-specific nitric oxide donors that deliver high amounts of nitric oxide and reactive species to clinical resistant tumors may be extremely useful in treating human tumors overexpressing ABC transporters.” [Source: NCI / PMC — Sinha et al., Cancers 2021] A separate PubMed study on NO-stimulated nanosystems for MDR cancer therapy confirmed the same mechanism: NO can reverse MDR by reducing P-glycoprotein (Pgp) expression, creating a more favorable microenvironment for drug delivery. [Source: PubMed/NIH] Drug resistance is behind an enormous share of cancer treatment failures. Research showing that NO could potentially unlock resistant tumor cells to existing drugs is one of the reasons this field has so much momentum.
The leap from lab findings to clinical treatment is never quick in oncology. Here’s an honest picture of where NO-based cancer therapy sits right now.
Nitroglycerin (NTG) — yes, the same compound used for over a century to treat angina — is also an NO donor, and it has been investigated across several cancer types. A 2023 comprehensive review published in Cell Death & Disease (Nature) summarized clinical trial work on NTG in non-small cell lung cancer (NSCLC), prostate cancer, liver cancer, and rectal cancer. Among the documented findings: a slow-release transdermal GTN patch showed a positive response in men with prostate tumors whose disease was progressing after surgery or radiotherapy. [Source: Nature / Cell Death & Disease – Meunier et al., 2023] The NIH’s own analysis confirmed: “GTN has also been shown to exhibit a positive response in combination with vinorelbine and cisplatin” (in NSCLC), and a slow-release transdermal GTN patch “has also been shown to be effective in men with prostate tumors whose disease was progressing following surgery or radiotherapy.” [Source: PMC/NIH]
At the AACR Annual Meeting 2023, Beyond Cancer, Ltd. presented preclinical data showing that intratumoral administration of ultra-high concentration nitric oxide (UNO) was more efficacious than anti-mPD-1 therapy in a murine breast cancer model, and demonstrated evidence of mPD-L1 upregulation, suggesting UNO may sensitize tumors to checkpoint therapy. [Source: BioSpace / AACR 2023]
The challenge with NO therapy has always been delivery, NO diffuses rapidly and doesn’t stay where you put it. That’s driving heavy research into nitric oxide-driven nanotherapeutics: engineered nanoparticles designed to deliver high NO concentrations directly to tumor tissue. Research published in the Journal of Controlled Release (2023) and reviewed in Journal of Nanobiotechnology (2024) outlined the latest advances, including tumor microenvironment-responsive systems that release NO only when they reach the specific chemical conditions inside a tumor. [Source: PubMed / Journal of Controlled Release, 2023 | Springer Nature / Journal of Nanobiotechnology, 2024] This is still experimental. Most of these systems have not yet moved into large-scale human trials. But the pace of publication in this space has accelerated significantly since 2021.
The clinical NO research above is about therapeutic delivery in a medical setting. But there is a separate, and equally important, conversation about what nitric oxide does for immune function day to day. As noted in multiple NIH-published reviews, NO is produced by immune cells including macrophages, neutrophils, and natural killer (NK) cells. It plays a direct role in how these cells identify and destroy pathogens and abnormal cells, including cancer cells in early stages, before a tumor is even established. The problem is that NO production declines with age. Research published in PMC (NIH) confirms that “enzymatic production of NO declines steadily with increasing age in healthy human subjects.” This immune function decline is one of the reasons older adults are significantly more vulnerable to both cancer and infection. [Source: PMC/NIH]
Supporting the body’s natural NO production through diet and lifestyle is a scientifically grounded wellness practice, separate from therapeutic NO delivery, but related in principle.
Diet: Beets, leafy greens (spinach, arugula, kale), watermelon, garlic, and nuts all support NO production through the dietary nitrate-nitrite-NO pathway or by supplying Larginine and L-citrulline.
Exercise: Even moderate aerobic activity stimulates eNOS activity in blood vessel walls. Avoiding smoking: Smoking is one of the most significant suppressors of NO bioavailability in the body
For adults over 40, who are already experiencing a measurable decline in natural NO production, maintaining adequate NO levels requires deliberate attention. Real Science Nutrition’s Immune Boost+ is formulated specifically with this in mind. It’s designed to support the body’s natural nitric oxide production and immune defense function, recognizing the well-documented relationship between aging, declining NO output, and immune vulnerability. As with any supplement, anyone managing a health condition should talk to their doctor before adding it to their routine.
Nitric oxide and cancer treatment is a legitimate, active, and complex area of science. Here’s what the research clearly supports: At low concentrations, NO can help tumors grow and survive. At high concentrations, it becomes cytotoxic to cancer cells, triggering apoptosis, reversing drug resistance, and potentially improving the effectiveness of existing treatments. Clinical investigation of NO-based therapies, through nitroglycerin, novel NO donors, and nanotherapeutic delivery systems, is ongoing across multiple cancer types. Results are promising but still developing. What is not in question is NO’s fundamental role in immune function, and the measurable decline in NO production that comes with age. Supporting those levels through diet, lifestyle, and, where appropriate, supplementation is a sensible, evidenceinformed approach to long-term immune health.