Tirazone (tirapazamine) / Teclison, SRI International - LARVOL DELTA

B-cell maturation antigen -targeted Tirapazamine-loaded liposomes overcome hypoxia-induced drug resistance and metastasis in multiple myeloma. (PubMed, J Control Release) - "In a relapsed/refractory MM mouse model, BCMA-targeted TPZ-loaded liposomes significantly reduced tumor progression while minimizing body weight loss in mice and reducing cytotoxicity in PBMCs, achieving a Efficacy-to-Body-Weight Toxicity Ratio of 8.3 compared to 1 for free TPZ. This study provides preclinical proof-of-concept for using BCMA-targeted TPZ-loaded liposomes as a promising and safer therapeutic option for relapsed/refractory MM."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Ultrasound-Activated Nanoinhibitors Blocking the Chemo-Immune Checkpoint to Overcome Chemotherapy-Induced Immune Resistance. (PubMed, Adv Sci (Weinh)) - "To address this, we fabricate an ultrasound-activated nanoinhibitor (Sono-TT8) that co-delivers tirapazamine (TPZ) and siXkr8 using a TiO2-derived sonosensitizer functionalized with the tLyP-1 peptide for active targeting of neuropilin-1 (NRP-1)-overexpressing tumor cells...Furthermore, Sono-TT8 exhibits superior tumor suppression and synergizes with αPD-L1 to inhibit metastatic progression. Our work establishes a chemo-immune checkpoint blockade strategy to overcome immune resistance in breast cancer, offering a nanosensitization approach compatible with multiple clinical treatment modalities."

IO biomarker • Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • NRP1

Calcification-Mediated Dual-Starvation and Immune Activation for Transarterial Chemoembolization. (PubMed, Int J Nanomedicine) - "We developed a thermosensitive PND nanogel co-encapsulating tirapazamine (TPZ) and folic acid (FA), TPZ/[email protected] vivo, TPZ/FA@PND delivered via TACE achieved complete embolization, induced marginal calcification, reduced metastasis, inhibited VEGF and MMP-9 expression, enhanced CD8+ T-cell infiltration, and promoted systemic antitumor immunity. This dual-starvation nanogel strategy integrates embolization, calcification-mediated containment, and immune activation, offering a clinically translatable approach to improve the therapeutic efficacy and long-term outcomes of TACE for HCC."

Journal • Hematological Disorders • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • MMP9

Cerenkov radiation modulates the extracellular matrix for improved pancreatic cancer chemotherapy. (PubMed, Cell Biomater) - "We developed a strategy to modulate the extracellular matrix (ECM) in pancreatic cancer to enhance chemotherapy through sequential administration of TiO2 nanoparticles (NPs), [68Ga] Ga-FAPI-04 ([68Ga]Ga-FAPI), and the chemotherapeutic drug tirapazamine (TPZ)...Additionally, CR-PDT consumes oxygen throughout the process, intensifying tumor hypoxia, which further activates TPZ, a hypoxia-activated and bio-reductive prodrug. Our design of CR-PDT-mediated ECM modulation brings new ideas for the exploration and application of radiotracer-combined nanomedicine in cancer therapy, particularly for cancers with abundant ECM."

Journal • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Solid Tumor • CAFs

Tirapazamine sensitises hypoxic homologous recombination-proficient NSCLC to PARP inhibition. (PubMed, Cell Death Discov) - "Here, we show that the hypoxia-activated prodrug tirapazamine (TPZ) synergises with the PARPi talazoparib to induce cytotoxicity in HR-proficient non-small cell lung cancer (NSCLC) cells, with preferential activity under hypoxia. In subcutaneous xenografts, the combination similarly suppressed tumour growth in the highly hypoxic A549 and CORL105 models, while showing minimal efficacy in the less hypoxic Calu-3 and H3122 tumours. This study highlights the potential of hypoxia-targeted DNA-damaging agents to expand PARPi utility to HR-proficient cancers and demonstrates that hypoxia enhances the therapeutic effect of this combination."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

New frontiers in anti-cancer drug testing: The need for a relevant In vitro testing model. (PubMed, NAM J) - "Hence, the spheroid models, which offer a three-dimensional structure more accurately mimic the natural tumor environment enhancing the study of drug interactions and cellular responses. This review focuses on the various anti-cancer drugs such as 5-Fluorouracil (5-FU), Tirapazamine (TPZ), Cisplatin, Resveratrol, Irinotecan and Doxorubicin that are tested in traditional monolayer cell culture and Spheroid models for comparing the efficacy and toxicity results in both using various analytical methods which helps us understand each method's advantages and limitations in drug development."

Journal • Preclinical • Review • Oncology

Sulforaphane Enhances Cytotoxic Effects of Non-Thermal Plasma and Tirapazamine Combination Therapy in Pancreatic Adenocarcinoma Cells. (PubMed, Cells) - "Sulforaphane-mediated enhancement occurred without restoration of connexin 43 expression or coordinated reversal of epithelial-to-mesenchymal transition markers, and treatments did not induce N-cadherin upregulation or suggest acquisition of invasive characteristics. Together, these findings support NTP + TPZ as a potent combinatorial strategy for pancreatic adenocarcinoma and identify sulforaphane as an effective adjunct that enhances cytotoxic efficacy through mechanisms that remain to be fully elucidated."

Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • CDH2 • GJA1

Multi-Branched Au Nanodendrite@ZIF-67 Loaded with Tirapazamine for Tumor Microenvironment-Activated Disruption of Cancer Organoids. (PubMed, ACS Appl Mater Interfaces) - "These combined actions synergistically amplify intracellular reactive oxygen species generation and disrupt mitochondrial membranes, leading to the selective elimination of tumor cells. This work presents a highly efficient, tumor microenvironment-responsive nanotherapeutic platform and demonstrates the critical value of organoid-based evaluation systems in advancing the clinical translation of targeted nanomedicines."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

Upconversion-near infrared persistent luminescence nanoplatform for triple-negative breast cancer photodynamic therapy and deep tissue imaging (ESMO-BC 2026) - "Subsequently, the PS Rose Bengal (RB) and the hypoxia-activated prodrug Tirapazamine (TPZ) were loaded onto ZGSCYH@MS, forming ZGSCYH@MSRT. In our study, we present a novel imaging-PDT platform based on ZGSCYH, which exhibits both NIR PersL and UCL properties... Overall, ZGSCYH@MSRT combines the imaging advantages of NIR-PersL with the therapeutic potential of UCL-based PDT. This imaging-PDT nanoplatform could offers a new strategy for integrated diagnosis and treatment of TNBC."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Molecular understanding for therapeutic targeting of hypoxia in breast cancer. (PubMed, Expert Opin Ther Targets) - "Apart HIF itself, other potential molecular targets such as prolyl-hydroxylases (PHD), von Hippel-Lindau protein (VHL), monocarboxylate transporters (MCTs), Na+ /H+ exchangers (NHEs), vacuolar ATPases (V-ATPase), anion exchangers (AEs), Na+ /HCO₃- co-transporters (NBCs), vascular endothelial growth factor (VEGF) and carbonic anhydrases were identified as being involved in tumorigenesis. HIF-1α inhibitors (topotecan, digoxin, PX-478), hypoxia-activated prodrugs (evofosfamide, apaziquone, porfiromycin, tirapazamine, banoxantrone) and carbonic anhydrase IX/XII inhibitors (SLC-0111) are either used clinically or in clinical development for the management of hypoxic breast cancers."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • Von Hippel-Lindau Syndrome • CA9 • HIF1A

KEYNOTE-A91: TATE and Pembrolizumab (MK3475) in mCRC and NSCLC (clinicaltrials.gov) - P2 | N=110 | Recruiting | Sponsor: Teclison Ltd. | Trial completion date: Dec 2025 ➔ Sep 2027 | Trial primary completion date: Dec 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A tirapazamine-assembled phototherapy agent for combined chemotherapy, photodynamic therapy, and photothermal therapy of hepatocellular carcinoma in mice. (PubMed, J Mater Chem B) - "In a HCC-bearing mouse model, TPZ@ITCC NPs enable fluorescence visualization and tumor-localized heating under 635 nm irradiation and achieve significant tumor suppression with no obvious systemic toxicity. TPZ@ITCC NPs therefore provide a single-wavelength-activatable nanoplatform that integrates tumor-localized PDT/PTT with hypoxia-activated chemotherapy for treating hypoxic HCC."

Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor

Dose-defining Study of Tirapazamine Combined With Embolization in Liver Cancer (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: Teclison Ltd. | Trial completion date: Dec 2025 ➔ Sep 2028 | Trial primary completion date: Dec 2025 ➔ Mar 2028

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor

TATE-PD1: Combination of TATE and PD-1 Inhibitor in Liver Cancer (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: Teclison Ltd. | Trial completion date: Dec 2025 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Gastric Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Tirapazamine sensitizes homologous recombination-proficient cancers by enhancing DNA damage andferroptosis (AACR 2024) - "In addition, the combination treatment significantly inhibited the growth of A549 and CORL105 xenografts that possess significant hypoxic fractions, but did not significantly inhibit the growth of well-oxygenated Calu3 and H3122 xenografts. Taken together, this study demonstrates that TPZ can sensitize HR-proficient tumor cells to PARPi through the introduction of DNA strand breaks and free radicals, suggesting that TPZ treatment can broaden the usage of PARPi to HR-proficient cancers."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Sulforaphane enhances cytototoxic effects of novel non-thermal plasma and Tirapazamine combined therapy in pancreatic adenocarcinoma cells (AACR 2025) - "However, the Western blots show inconsistent loss of vimentin, consistent loss of E-cadherin, and no upregulation of Cx43. While these results suggest SF has potential as an adjunct agent, further investigation is needed to understand the causes of increased cytotoxicity between SF and NTP+TPZ in pancreatic adenocarcinomas."

Brain Cancer • CNS Tumor • Glioblastoma • Melanoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CDH1 • VIM

Oxygen-Adaptive Covalent Organic Framework Nanoarchitectonics with High Photothermal Conversion Efficiency for Quadruple-Modal Tumor Therapy. (PubMed, Adv Healthc Mater) - "Remarkably, GTPZ exhibits a record-high photothermal conversion efficiency of 72% among COF-based nanomedicines, enabling spatiotemporal control over hypoxia-activated tirapazamine (TPZ) release to generate cytotoxic radicals...In MCF-7 models, GTPZ achieves high tumor suppression through synergistic lipid peroxidation, cell cycle arrest, and ferroptosis. This work provides a paradigm for designing intelligent nanomedicines capable of dynamically adapting to TME."

Journal • Oncology

Cholesterol Metabolism Regulated Nanoliposome Ameliorates Chemo/Photothermal Therapy Reversing CD8+ T Cell Exhaustion. (PubMed, Exploration (Beijing)) - "Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses...When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor

Rationally designed thiazole-based COF with multiphoton activity for drug delivery and synergistic therapy of deep-seated tumors. (PubMed, J Nanobiotechnology) - "Furthermore, tirapazamine (TPZ), a hypoxia-activated chemotherapeutic drug, was encapsulated into DT-COF pores with anastomosing dimensions (drug loading efficiency = 76.2%)...Additionally, DT-COF consumed the limited intratumoral oxygen to generate singlet oxygen, which further cooperated with the hypoxic tumor microenvironment to promote the activation of TPZ, thereby achieving synergistic antitumor therapy through the combination of photodynamic therapy and chemotherapy. This study provides a new strategy for the development of MPAPSs and demonstrates their potential in cancer theranostics."

Journal • Oncology • PAPSS1

A phase 2, open-label single-arm, multi-center study of trans-arterial tirapazamine embolization (TATE) combined with nivolumab (nivo) in patients with advanced immunotherapy-refractory hepatocellular carcinoma (HCC). (ASCO-GI 2026) - P2 | "TATE plus nivo is promising in the salvage setting of advanced HCC patients who failed at least one line of immunotherapy. Further investigation is warranted to confirm the efficacy of this combination. Best overall response in all evaluable patients."

Clinical • IO biomarker • Metastases • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

PISTOL MRI allows noninvasive assessment of changes in tumor oxygenation post hypoxia targeted therapy. (PubMed, Sci Rep) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Hydroxylated dendrimer nanogels co-deliver drugs and cytokines for chemoimmunotherapy of glioma. (PubMed, Mater Today Bio) - "Herein, we develop a dual pH/reactive oxygen species-responsive dendrimer nanogel (DNG) platform based on generation 3 poly(amidoamine) (G3 PAMAM) dendrimers for co-delivery of the hypoxia-activated prodrug tirapazamine (TPZ) and the immunomodulatory cytokine interferon-gamma (IFN-γ)...Leveraging the rich hydroxyl groups and the enhanced permeability and retention effect of DNGs, the DNGs-TPZ/IFN-γ can penetrate the BBB and demonstrate potent therapeutic efficacy in an orthotopic mouse glioma model. The developed DNGs-TPZ/IFN-γ with a simple composition may be developed to co-deliver drugs and cytokines to tackle other cancer types."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • IFNG

NIR-light triggered photodynamic therapy combined with hypoxia activated chemotherapy for anti-tumor effects. (PubMed, Nanoscale) - "To overcome these limitations, we rationally designed a composite upconversion nanoparticle, UCNPs@MSN-Ce6/TPZ (UMCT), integrating the photosensitizer chlorin e6 (Ce6) and the hypoxia-activated prodrug tirapazamine (TPZ) for synergistic PDT and chemotherapy...Significantly, UMCT shows effective accumulation at the tumor site, achieving a potent and synergistic tumor-suppressing effect both in vitro and in vivo. This work provides a promising strategy for designing more efficient PDT nanoplatforms and advancing their biomedical applications."

Journal • Oncology

Facile Preparation of Nanoscale Chlorin-Integrated Covalent Organic Frameworks for Combined Chemophototherapy. (PubMed, Biomacromolecules) - "The optimized TPCCOF morphology was used to load tirapazamine (TPZ), forming the biocompatible TPCCOF@TPZ nanoplatform...This synergistic PDT/PTT/chemotherapy combination effectively suppresses 4T1 tumor cell proliferation under both normoxic and hypoxic conditions. Our work advances nanoscale COF design for multimodal cancer therapy and supports preclinical development of porphyrin-based photosensitizers."

Journal • Oncology

Microbiota-directed lactic acid depleting nanoenzyme reactivates antitumor immunity and chemosensitivity in hypoxic tumor. (PubMed, Mater Today Bio) - "To tackle this challenge, we engineered a delivery platform (TML NPs) for lactate oxidase (LOX) and chemotherapeutic drug tirapazamine (TPZ) by modifying the carrier with metronidazole (MTZ), an antibiotic bearing hypoxia-responsive functional group. By directly targeting the symbiotic anaerobic bacterial metabolism, this strategy introduces a novel paradigm for modulating TME acidification, reversing the LA-mediated suppression of anti-tumor immune responses and chemosensitivity. Our strategy offers a promising translational platform for the precise treatment of TNBC and other hypoxic malignancies."

Journal • Oncology • Triple Negative Breast Cancer