Something quiet happened in a laboratory in Finland last week. A research team was studying a class of drugs that millions of people take for a very ordinary problem, and they found something that had no business being there. The drugs had been doing something else entirely, something their creators never designed them to do, and something that, if it holds up under clinical scrutiny, could matter enormously to one of the hardest groups of patients to treat in modern medicine.
The drugs in question are used every day to manage anemia – the condition where the blood simply doesn’t carry enough oxygen to keep the body functioning well. The patients who need them most are those with chronic kidney disease, a population that struggles to produce enough red blood cells because their kidneys can no longer send the right signals to the body. For these patients, this class of medication has been a genuine step forward. But cancer? That was never part of the conversation.
Until now. A study published this spring has upended the assumed boundaries of what these drugs can do. The findings raise serious questions, open genuine possibilities, and sit at the intersection of two of the most challenging conditions in medicine. What researchers found was not what anyone expected, and the implications stretch well beyond the kidney ward.
What HIF-PHIs Are and How They Work
The medications at the center of this story, known as HIF-PHIs (hypoxia-inducible factor prolyl hydroxylase inhibitors), are currently used to help patients with chronic kidney disease produce more red blood cells. The name is a mouthful, but the mechanism is elegant. They work by stabilizing proteins that help cells respond to low oxygen levels.
To understand that more plainly: when oxygen drops in the body, a family of proteins called hypoxia-inducible factors (HIFs) normally spring into action and tell the body to produce more red blood cells. In healthy people, this system self-regulates. In people with chronic kidney disease, the signaling breaks down. HIF-PHIs essentially prop open the oxygen-sensing alarm system, allowing it to stay active even when it would normally be switched off. Their therapeutic mechanism involves stabilizing HIF-alpha, thereby stimulating erythropoietin production and regulating iron metabolism. Erythropoietin, or EPO, is the hormone that commands the bone marrow to make red blood cells.
By inhibiting prolyl hydroxylase domain (PHD) activity, these drugs stabilize HIF transcription factors, enhancing their transcriptional activity. Their pharmacodynamic effects are dose-dependent and protocol-specific. Practically speaking, a patient takes a pill instead of receiving injections. This oral approach offers a potential advantage over traditional erythropoietin injection therapies, which require regular clinical visits.
More specifically, HIF-PHIs reversibly inhibit HIF-PHD dioxygenases, enzymes that utilize molecular oxygen for hydroxylation – a chemical process that, when disrupted, allows the HIF proteins to accumulate and drive red blood cell production. And they do more than just stimulate red cell production. HIF-PHIs stimulate endogenous EPO synthesis, reduce hepcidin levels, and boost iron utilization – hepcidin being the hormone that limits how much iron the gut absorbs. Lower hepcidin means more iron gets into circulation, which in turn supports healthier red blood cell production.
The Scale of the Problem They Already Solve
Before exploring what these drugs may do in cancer, it is worth anchoring the conversation in the problem they were built to solve. Nearly 4.8 million people in the United States are affected by anemia in the context of chronic kidney disease. Managing anemia in that population requires consistent, long-term treatment, often for years or even decades.
The regulatory history of these drugs reflects both their promise and the cautious pace of medical approvals. The FDA approved daprodustat as the first oral treatment option for anemia in dialysis-dependent chronic kidney disease patients – a meaningful milestone, since prior treatments required injections. Four compounds are approved for marketing in Japan, including daprodustat and roxadustat, for dialysis-dependent CKD. Roxadustat’s story with the FDA has been more complicated. The FDA’s decision not to approve roxadustat followed a vote from the agency’s advisory committee that the drug’s benefit-risk profile did not meet the bar for approval in the United States for CKD anemia, though it is approved in Europe, Japan, and dozens of other countries.
That makes recent regulatory movement in a different direction particularly striking. The FDA granted roxadustat an Orphan Drug Designation for the treatment of myelodysplastic syndromes, announced in December 2025. Myelodysplastic syndromes (MDS) are blood cancers in which the bone marrow fails to produce enough healthy blood cells – a condition where anemia is also a central, debilitating feature. This designation signals that regulators are paying attention to HIF-PHIs’ potential reach beyond kidney disease.
The Finnish Discovery: What Changed
New research published in May 2026 found that common anemia medication cancer researchers were studying may also slow down cancer cell growth. Researchers from the University of Oulu and the University of Eastern Finland discovered that these drugs affect cell metabolism and growth in ways previously unknown.
The findings, published in Redox Biology, suggest that the drugs could benefit cancer patients who often suffer from anemia, potentially treating two problems at once.
The research was led by Professor Thomas Kietzmann from the Hypoxia and Extracellular Matrix Research Unit at the University of Oulu. What his team found shook a long-held assumption about how HIF-PHIs operate. The prevailing view was that these drugs worked exclusively through the HIF-1alpha and HIF-2alpha proteins – the oxygen-sensing proteins they were designed to stabilize. That turned out to be only part of the story.
The research team found that the drugs also influence cell growth and blood vessel formation even when these specific oxygen-sensing proteins are not present. In plain terms: the drugs were stopping cancer cells from growing and cutting off their blood supply through an entirely separate mechanism – one that scientists had not accounted for.
Kietzmann stated that his team has the mechanistic data but needs clinical expertise to move forward. He encouraged oncologists and clinicians interested in tumor anemia to collaborate. “Initiating clinical trials could reveal a dual advantage for patients,” he said. “This is exactly the kind of teamwork that can change patient care.”
The study, published in Redox Biology with the title “Clinically approved HIF-PHIs modulate redox metabolism, cell growth, and angiogenesis independent of HIF-1α/HIF-2α,” was funded by the Research Council of Finland, the Jane and Aatos Erkko Foundation, and the Finnish Profi6 “Fibrobesity” program. Because the Redox Biology DOI originally cited in this piece (https://doi.org/10.1016/j.redox.2026.104206) carries a future-dated identifier that could not be independently verified at publication, we are not linking to it directly. The journal and title details are provided above for readers who wish to search for the article.
Anemia in Cancer Patients: A Problem Hiding in Plain Sight
To grasp why this discovery matters so much, consider the position cancer patients are in before treatment even begins – or while it is underway. Chemotherapy-induced anemia develops when chemotherapy drugs damage bone marrow cells that create red blood cells, reducing oxygen circulation throughout the body. About 70% of people receiving chemotherapy develop this condition. That is a staggering proportion. Common symptoms include fatigue, shortness of breath, rapid heart rate, dizziness, and pale skin – and these symptoms often overlap with cancer symptoms themselves, making management complex.
Many cancer patients suffer from anemia caused by the tumor or by chemotherapy. Currently, treating the anemia and fighting the tumor are separate goals – requiring separate drugs, separate dosing schedules, and often conflicting risk considerations. If a single agent could address both simultaneously, the benefit to patients would not just be additive. It could also reduce the complexity and toxicity of treatment regimens that are already difficult to tolerate.
That dual-action possibility is exactly what a 2025 review published in Frontiers in Pharmacology was grappling with, noting that recent clinical studies have demonstrated that roxadustat exhibits efficacy comparable to that of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy-induced anemia. ESAs – drugs like epoetin and darbepoetin – have been the standard tool for managing this problem, but they carry their own concerns, including the possibility of stimulating tumor growth.
Read More: Signs Your Kidneys May Be Struggling
The Cancer Connection: Promising Evidence, Real Cautions
The idea that HIF-PHIs might have anti-cancer properties is not entirely without prior support. Earlier laboratory research found that amplifying HIF signals with the prolyl hydroxylase inhibitor roxadustat significantly suppressed glioblastoma (a type of aggressive brain cancer) cell growth, particularly in cells that were resistant to standard chemotherapy. The accumulation of lipid peroxidation and cellular iron in cancer cells following treatment indicated that the cells underwent ferroptosis – a form of cell death driven by iron-dependent oxidative damage.
A Phase II clinical trial also found that roxadustat increased hemoglobin levels from baseline to week 16 by a mean maximum of 2.4 to 2.5 g/dL in patients with chemotherapy-induced anemia – a clinically meaningful improvement that matched or exceeded what existing injectable therapies typically achieve, and in an oral, more convenient format.
On the regulatory side, the FDA supported the advancement of roxadustat for the treatment of patients with anemia-associated lower-risk myelodysplastic syndrome, agreeing upon important design elements for a pivotal Phase 3 trial in a Type C meeting with the drug’s developers. A Phase III randomized, open-label, controlled study also evaluated the efficacy and safety of roxadustat for the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies – further evidence that the clinical community is taking this application seriously.
But the scientific picture is genuinely complex, and intellectual honesty demands saying so. Preclinical studies show that HIF-1alpha activation promotes tumor progression through multiple pathways, including metabolic reprogramming, angiogenesis, metastasis, and immune evasion. Current evidence shows no increased malignancy risk with roxadustat in renal patients. However, tumor progression events were reported as treatment-emergent serious adverse events in chemotherapy-induced anemia studies, and clinical data linking roxadustat to tumor progression remain limited.
The observation periods in these studies have been short, and a causal relationship between HIF-PHI use and tumor progression remains unestablished due to the insufficient duration of observation required to adequately assess potential HIF-driven oncogenic risks.
This is the central tension: the same biological pathway that might help suppress cancer cell growth under the new Finnish findings could, through a different mechanism or in a different cancer type, theoretically support tumor growth. Patients with a history of cancer within the prior two to five years were excluded from clinical trials for HIF-PHIs due to precisely these safety concerns. The ASCEND-ND trial – one of the largest daprodustat trials conducted, registered with ClinicalTrials.gov – found that cancer-related adverse events were numerically more frequent in the daprodustat arm compared to the darbepoetin arm in prespecified on-treatment analyses, though post-hoc analyses published in Nephrology Dialysis Transplantation found that this apparent imbalance largely reflected differences in how long patients in each arm were followed after their last dose, and that results moved closer to neutrality once those dosing interval differences were accounted for. Causality was not established.
What the Finnish research contributes to this picture is a mechanistic explanation for why the drugs might behave differently in cancer contexts: because their effects on cell growth and blood vessel formation do not depend solely on the HIF pathway. That opens the possibility that specific HIF-PHI compounds or dosing strategies could be optimized to maximize the anti-cancer effect while minimizing the pro-tumor risk.
Where the Science Stands Now
HIF-1 plays a pivotal role in tumor biology, particularly in hypoxic environments. Over the past few decades, a number of HIF-1 inhibitors have been identified as potential therapeutic agents for various cancers. However, none of these inhibitors have been successfully translated into clinically available cancer treatments – a fact that underscores both the promise of this pathway and the difficulty of converting laboratory excitement into proven therapies.
The Finnish findings do not change that reality overnight. What they do is add mechanistic weight to a hypothesis that is already gathering clinical momentum. They suggest that at least part of what these drugs do inside a cancer cell happens independently of the HIF proteins, which means scientists now have a new set of targets to investigate, a new rationale for testing these drugs in oncology settings, and a new argument for the collaborative clinical trials that Professor Kietzmann is calling for.
Recent clinical studies have demonstrated that roxadustat exhibits efficacy comparable to that of erythropoiesis-stimulating agents in the management of chemotherapy-induced anemia – which means that even if the anti-cancer effects take years to establish, the immediate case for testing these drugs in cancer patients managing anemia is already strong.
Meanwhile, the results of the MATTERHORN study, a Phase III randomized, double-blind, placebo-controlled trial exploring the efficacy and safety of roxadustat for treating anemia in patients with lower-risk myelodysplastic syndromes, demonstrated that roxadustat was well tolerated in that population – an important safety signal for a drug being considered in people who are already fighting a blood cancer.
What to Do With This Information Now
This research is not a treatment recommendation. No doctor today will prescribe a HIF-PHI to fight cancer based on a single study – nor should they. The gap between a compelling laboratory or early-clinical finding and an approved, evidence-backed therapy is wide, and it is measured in years, not months.
What this finding does represent is a serious scientific signal. A class of drugs already inside the medical system, already proven safe enough to take long-term for kidney disease, and already available in oral form, may have a second act in oncology. Drug repurposing – finding new uses for existing medications – is one of the most efficient paths in medicine, because much of the hard safety work is already done.
For patients currently managing anemia alongside a cancer diagnosis, the most practical takeaway is this: talk to your treatment team about what is driving your anemia and what options exist. If you are receiving chemotherapy and developing anemia, treatment options may include blood transfusions, erythropoietin-stimulating agents, and iron or vitamin supplements – and as the evidence base grows, HIF-PHIs may soon join that list in a more formal way.
For clinicians and researchers reading this, Professor Kietzmann’s call for oncology collaborators is explicit and urgent. The mechanistic data exists. What comes next requires people with the clinical expertise to design and run the trials that can turn a laboratory discovery made in Oulu, Finland into a tool that actually changes what happens in a treatment room. The biology is compelling. The safety questions are real. The next chapter will be written in clinical trials – and if those trials succeed, patients carrying two burdens at once may one day need only one drug to address both.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis, or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.
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