The impossible is becoming possible
Recent developments are showing that advanced-stage cancer involving an aggressive cancer with multiple secondary tumours around the body no longer needs to be the incurable disease that surgery, chemotherapy and radiotherapy once were unable to stop.
In the most exciting advance to happen in 50 years of cancer treatment in the modern age, there is hope, at least for some patients.
That hope is called an abscopal response. This is where a small number of tumours (usually 1 or 2) are exposed to radiotherapy with the aim of shrinking them, only to find that not just the irradiated tumours shrink, but the tumours outside of the irradiation zone in distant parts of the body also respond by shrinking or even disappearing.
An abscopal response in a patient with a leiomyosarcoma, a rare form of cancer. The primary cancer was in the abdomen with secondary tumours in the lungs. Three months after the primary tumour was exposed to a low dose of radiotherapy in conjunction with treatment with VeyondaÒ, this X-ray shows one of the secondary lung tumours shrinking by 80% despite not receiving any radiotherapy.
Up until recently the abscopal response was an extremely rare phenomenon. Just a handful of patients in 50 years of radiotherapy were reported to have had such a response.
All that changed about 15 years ago with the introduction of the so-called immuno-oncology drugs (the PD-1 and PD-L1 inhibitors). Originally these drugs were meant to be used on their own to break down the barrier that stopped the body’s immune system from being able to reach into tumours to kill the cancer cells. And about 10-20% of patients with certain types of cancer such as lung, bladder and kidney cancers and melanoma, responded, some on a long-term basis.
But then these immuno-oncology drugs began to be used in conjunction with radiotherapy, and suddenly abscopal responses started showing up in between 20-25% of patients. In most cases the responses were not curative - a partial response (shrinking, but not completely disappearing) and only lasting temporarily (months to several years) – but nevertheless offering longer life in patients facing poor prognoses. But in some cases the responses were complete (all tumours disappearing) and long-term, raising the prospect of being ‘cured’.
The reasons for an abscopal response remain obscure, although three events seemingly
need to happen. The first is that the cancer cells need to be damaged or killed by radiation. That seems to be the key trigger point for the second event which is the release of chemical signals into the blood that press the self-destruct button in other cancer cells. The third event which appears to need the presence of a drug, is activation of the the body’s immune system to clean up residual cancer cells. Together, these 3 events result in a tsunami-like cascade of death of tumour cells all around the body.
Veyonda® is a next generation immuno-oncology drug that compared to the current generation of immuno-oncology drugs holds the promise of delivering
- a higher rate of abscopal response
- across more types of cancer
- providing a longer-lasting effect
- with a much higher degree of safety
- and at a considerably lower cost.
- the Noxopharm drug candidate previously known as NOX66 now has the registered trademark Veyonda®
Veyonda® works in 3 unique ways, all related to its function as an inhibitor of protein tyrosine kinases:
- Veyonda® makes the cancer cell more sensitive to radiation
By inhibiting cyclin dependent kinases, Veyonda® is cytostatic, meaning that it blocks cancer cells from dividing, holding them in a phase of cell division known as G2M where the cell’s DNA is at its most susceptible to damage by radiation = cancer cells more likely to be lethally damaged by radiotherapy.
- Veyonda® makes the cancer cell less able to repair radiation damage
Radiation works by inflicting damage on a cell’s DNA. The cell seeks to repair the damage and will survive if it is successful. The aim of radiotherapy is to inflict more damage than can be repaired.
By inhibiting sphingosine kinase and PI3 kinase (thereby blocking DNA-repair enzymes, PARP-1 and topoisomerase 1 and 2), Veyonda® effectively blocks the ability of the cancer cell to repair its damaged DNA. This means that cancer cells that might otherwise repair the damage and survive radiotherapy now will be killed = more cancer cells being killed.
- Veyonda® activates the immune system
By modulating the src family of kinases regulating the role of spleen tyrosine kinase (SyK) in the activation of immune cells, VeyondaÒ belongs to a class of chemicals that activate the cells of the innate immune system, particularly natural killer (NK) cells which are the body’s first line of defence against cancer cells = an activated immune system able to attack and clear cancer cells from the body.