AQ4N activation in human tumours

Human evidence · Activation in tumour tissue

A presurgical study evaluated AQ4N in 32 patients with
solid tumours, including eight with glioblastoma. Patients
received a single dose before surgery, allowing researchers
to examine drug activation directly in tumour tissue.

AQ4, the active form of AQ4N, was detected in every tumour
sample analysed. Glioblastoma samples contained the highest
mean AQ4 concentration. Microscopy showed AQ4 within regions
expressing a marker of tumour hypoxia.

The study provides human evidence of tumour exposure and
hypoxia-selective activation. It was not designed to establish
whether AQ4N improves tumour control or survival.

Albertella MR et al. Clinical Cancer Research.
2008;14(4):1096–1104.

Read the published study

AQ4N: clinical dosing experience

Clinical experience · Dosing, safety and drug exposure

A Phase I study evaluated AQ4N alone in 16 patients with
advanced solid tumours. Repeated intravenous dosing provided
data on drug exposure, tolerability and dose selection.

Stable disease was recorded in three patients, including
one patient with collecting duct renal cancer whose disease
remained stable for 25 months. No objective tumour responses
were observed.

This small, uncontrolled study adds to AQ4N’s clinical
development foundation. Its principal purpose was to assess
dosing and safety; the disease-control observations do not
establish a treatment benefit.

Papadopoulos KP et al. Clinical Cancer Research.
2008;14(21):7110–7115.

Read the published study

OCT1002 in prostate cancer models

Preclinical research · Prostate cancer models

Two studies investigated OCT1002 in laboratory and mouse
models of prostate cancer, examining its ability to target
hypoxic tumour cells and complement existing treatments.

The first study demonstrated activation of OCT1002 within
hypoxic tumour regions. OCT1002 enhanced the antitumour effects
of bicalutamide and reduced expression of genes associated
with malignant progression.

A second study in castration-resistant prostate cancer
models found inhibition of tumour growth and disruption of
tumour blood vessels. In these models, OCT1002 also enhanced
the effects of abiraterone, docetaxel and cabazitaxel.

These preclinical findings support further investigation
of OCT1002 in prostate cancer.

Nesbitt H et al. Clinical Cancer Research.
2017;23(7):1797–1808.
Read the bicalutamide combination study

Nesbitt H et al. The Prostate.
2017;77(15):1539–1547.
Read the castration-resistant prostate cancer study

How AQ4N and OCT1002 target hypoxia

Scientific review · How uHAPs work

This review brings together the scientific rationale for
unidirectional hypoxia-activated prodrugs (uHAPs), including
AQ4N and OCT1002.

It explains how these compounds undergo irreversible
activation under hypoxic conditions, producing active drugs
that bind to DNA and target topoisomerase IIα, an enzyme
essential for cell division.

The review examines how this mechanism could complement
standard cancer treatments by targeting living hypoxic cells
that can resist therapy. It provides a scientific framework
for further clinical investigation.

Smith PJ, McKeown SR, Patterson LH. IUBMB Life.
2023;75(1):40–54.

Read the scientific review

Media coverage of OCT1002 research

Media coverage · Prostate cancer research

ITV News covered Ulster University’s research into combining OCT1002 with hormone therapy in preclinical prostate cancer models. Dr Declan McKenna discussed the findings and the potential to target treatment-resistant cancer cells.

The three-year research programme was supported by Prostate Cancer UK through a £213,000 grant from the Movember Foundation.

The underlying study was published in Clinical Cancer Research and forms part of the OCT1002 evidence described above.

ITV News / UTV. 31 October 2016.

Read the media report

Nesbitt H et al. Clinical Cancer Research. 2017;23(7):1797–1808.

Read the published study