An alternative universe in which our biggest enemy is seen for what it is

Imagine a world where good is evil and evil is good, where heroes are villains and villains are heroes, where beauty and intelligence are reviled, where the sun is blood red instead of yellow, and where everything is basically the same – only backwards and distorted.

This is a description not of the ten-day adult extravaganza called Fantasy Fest in Key West, Florida but of the alt comic reality known as Bizarro World, after its self-appointed ruler, Bizarro.

This character is a grotesquely inverted and misshapen clone of Superman; Bizarro, who wears a backwards ‘S’ on his chest, is a villain and nemesis of Superman with opposite powers like cold instead of heat vision.

According to Bizarro code, ‘Us do opposite of all Earthly things! Us hate beauty! Us love ugliness! Is big crime to make anything perfect on Bizarro World!’

The same basic premise is at work in an episode of Seinfeld called ‘The Bizarro Jerry’, where Elaine befriends the kinder, gentler look-alikes or doppelgangers of Jerry, George and Kramer only to be rejected by them for her disruptive, obnoxious, arrogant behaviour, which – of course – the real Jerry, George and Kramer tolerate.

Bizarro World is also a metaphor for cancer cells, which, like Superman’s nemesis, are warped clones of their normal counterparts that act completely contrary to them.
Where normal cells are mortal, cancer cells are immortal.

Where normal tissues are organised, cancer is extremely disorganised.

Where normal cells do not deviate from a narrow range of internal balance, a state known as homeostasis, cancer cells thrive under extreme, non-homeostatic conditions of acidic pH and low oxygen or hypoxia.

Where immune cells normally eliminate cancer cells, in tumours they support them.
Where blood flow is normally uniform and orderly, in tumours it is sluggish and disrupted.

And on and on.

The language used in oncology reflects this upside-down situation, where bad is good and good is bad.

For example, in everyday life, progression is normally a positive word, and regression is normally a negative one. As in ‘you’ve shown good progression at work or school (a positive)’. Or ‘you’ve regressed back to your bad habits (a negative)’.

However, in the contrary linguistics of cancer, progression refers to growth of tumours, which makes it a negative word that no patient wants to hear, and regression refers to tumour shrinkage, which makes it a positive one that is good to report.

Likewise, the term ‘pseudo progression’, which could be interpreted to mean ‘false progress’, in fact describes the false appearance of tumour progression on imaging, which, if confirmed, usually portends an excellent prognosis.

In cancer world, down is up and up is down.

In the Comics, Superman manages to stop Bizarro with Blue Kryptonite, which strengthens Superman (as opposed to the Green Kryptonite that poisons Superman and supercharges Bizarro).

Not to oversimplify and ‘cartoon-ise’ tumours, or to take inspiration from DC Comics per se, but since tumours are the literal opposite of normal tissues, it makes intrinsic sense that to eliminate them requires reorganisation or ‘normalisation’ of the abnormal conditions that are present – this is effectively their ‘Blue Kryptonite’.

For example, a landmark breakthrough in the treatment of cancer is the use of immunotherapy, which aims to make tumour-corrupted immune cells behave more like normal immune cells that stand up, not down, against cancer.

Many previously fatal tumours, such as melanoma and lung, bladder and kidney cancer, are now treatable thanks to immunotherapy.

Ditto for already approved vascular therapies that prune, rather than eliminate, the inefficient vessels of tumours, and so make blood flow and oxygen delivery more uniform and regular, which, in turn, renders tumours less aggressive and treatment resistant.

By contrast, the standard use of radiation and chemotherapy only make conditions in tumours more irregular – more acidic, more oxygen deprived, more poorly perfused with blood. This may in the end paradoxically strengthen not weaken the cancer cells, according to the Nietzschean – and Kelly Clarksonean – doctrine of ‘what does not kill me makes me stronger’.

This is to advocate not against the use of chemotherapy and radiation – they are certainly important and useful tools in the anti-cancer toolbox – but for therapies that first ‘fix up’ or ‘gentrify’ the Bizarro ‘neighbourhood’ that surrounds and supports tumours and, in so doing, making it easier for chemotherapy and radiation to access and eliminate cancer cells.

This neighbourhood comprises immune cells, blood vessels and other cells, like scar-producing fibroblasts.

Tumours are not exactly self-sufficient and closely depend on their neighbourhood for growth and survival; on their own, without the succour and support from these neighbourly interactions, tumours do not stand a chance.

Several biopharmaceutical companies like one that employs me called EpicentRx – feature late-stage ‘blue Kryptonite-like’ therapies such as RRx-001 (nibrozetone) and AdAPT-001.

Their purpose is to change the essential character of the neighbourhood in favour of disease control and improved responses to chemotherapy, radiation and immunotherapy.

The expression, ‘there goes the neighbourhood’ usually refers to the introduction of an undesirable element or elements, which will sooner or later lead to its downfall.  However, in the Bizarro world of cancer-speak, ‘there goes the neighbourhood’ is meant to signal its literal elimination with Blue Kryptonite therapies like RRx-001 (nibrozetone) and AdAPT-001.

As a result, these will hopefully predispose to the death of cancer cells both alone and in combination with other anti-tumor agents, and, in the process, make it easier for patients not only to survive but to thrive.