The new take-at-home drug that ‘could boost effectiveness of chemotherapy'
Named KCL-HO-1i, the drug operates by dismantling a crucial defence mechanism employed by tumours to shield themselves from treatment.
Initial trials conducted on mice demonstrated remarkable success, with the tablet enabling chemotherapy-resistant tumours to become responsive to therapy.
Researchers are now hopeful for human trials, envisioning KCL-HO-1i as a "valuable companion drug" to chemotherapy.
This could potentially spare patients from more aggressive interventions.
While chemotherapy remains a cornerstone in treating various cancers by disrupting cell growth, its efficacy can be hampered in some individuals when the body's immune cells inadvertently form a protective barrier around tumours.
These white blood cells, known as macrophages, produce a protein called heme oxygenase-1 (HO-1), which helps shield the tumour from the immune system and blocks the effects of chemotherapy.
KCL-HO-1i, which has been created by experts at King's College London (KCL), targets this protein to make tumours more responsive to treatment.
Professor James Arnold, head of tumour immunology group at the university, said: 'We discovered that these macrophages in cancer play a key role in blocking chemotherapy.
'By targeting the enzyme they produce using KCL-HO-1i, we were able to help beneficial immune cells and chemotherapy drugs become significantly more effective.
'In laboratory models, even chemotherapy-resistant tumours became responsive to treatment, which is a really exciting step forward.'
The drug has been designed for patients to take at home as a tablet between chemotherapy sessions.
Early tests on mice, published in the journal Science Translational Medicine, found the drug made breast cancer tumours more responsive to different types of chemotherapy.
Researchers are now hopeful that trials involving patients with breast cancer and other forms of the disease could begin within two years.
James Spicer, a professor of experimental cancer medicine at KCL, said: 'Chemotherapy remains a key part of treatment for many patients with cancer, but too often it is not as effective or long-lasting as we might like.
'This research has identified a key reason for these limitations, and discovered a drug that we are keen to test in the clinic alongside established chemotherapy drugs.'
Miraz Rahman, a professor of medicinal chemistry at KCL, added: 'If human trials are successful, KCL-HO-1i could become a valuable companion drug to existing cancer therapies – helping more patients to benefit from the treatments that are already available and reduce the need for more aggressive cancer therapies in the future.'
The King's College London scientists have launched a spin-out company called Aethox Therapeutics.
Tanya Hollands, research information manager at Cancer Research UK, which supported the study alongside funding from the Medical Research Council, said: 'Researchers are increasingly learning how to make better use of existing cancer treatments, whether it's using them differently or in combination with new medicines, like this work suggests.
'Using combination therapies can help bring improved treatment options to patients more quickly, safely and affordably, because some components of the treatment have already been tested and used in the clinic.
'While early stage, it's exciting to see this potential new way to disarm cancer's ability to avoid detection by the immune system with a new drug, while also boosting the effectiveness of chemotherapy, and we look forward to seeing how this work progresses.'
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