Cancer evolves, and so must the treatment.
Four alternative approaches to battling the most insidious of diseases
Some months back, I ran into an old friend of mine who I don’t see often these days. After the usual chitchat formalities of family, work, and health, she took a special interest in my latest diabetic report (I have type 1 diabetes). Her husband, who was not long retired and still living a very active life, had been recently diagnosed with type 2 diabetes, although he was coping well with treatment.
She then regaled me with tales of how he had spent over a year in decline, losing weight every month, drinking copious amounts of water and sleeping far more than usual, to the point where he was gaunt and seemed barely extant. It emerged during this discourse that ten months had passed between the emergence of his first symptoms and the point of diagnosis when his wife could take it no more and he was press ganged to the local doctor.
Reading the puzzlement in my face, and before I could get the ‘why did he wait…?’ out of my mouth, she cut me off and explained: “He thought he had cancer.”
I will let your obvious question hang here now.
As a child, I heard cancer referred to as ‘the lad’ or, among the more forthright, the ‘big C’. To my parents’ generation, it was so feared that people would never utter its name outright, almost as if the mere hint of it would draw cancer to one’s door. Or perhaps they felt it wouldn’t help to speak so openly of what was regarded as death sentence.
Not that this would make much difference. After all, the disease is rarely far from any of our doors, more so today than ever. Curiously, there are still sections of our older population who won’t go to see a doctor and absolutely will not attend a hospital. For them, doctors lead to hospitals, and hospitals are places from where you sometimes never leave. Cancer had a big part in all of those perceptions.
Thanks in part to the advances of modern medicine, most people diagnosed with cancer today can legitimately hold on to hope. They might still have the fear, but they wait for the prognosis after diagnosis, for the paths and options available to them. These options are available as a result of the research carried out in institutes that are dedicated to defeating cancer, and as a result of the societies and charities such as Cancer Research UK, the Irish Cancer Society and American Cancer Society who raise money to aid this research.
However, for all the latest breakthroughs we hear about from newspapers and news bulletins, between 1.5 million and two million people will receive a cancer diagnosis in the US this year alone. Of these, a third will die. That’s a sobering thought and one that leads many people to ask the question: why haven’t we cured cancer yet?
While the answer to that question is complex, the best response to my mind is to remember that cancer is not so much a single disease, but rather a collection of diseases. Uncontrolled proliferation of cells is the end result of many different underlying factors. Perhaps the most insidious thing about the disease is that cancer is also subject to evolutionary processes, as laid out by Charles Darwin in his concept of natural selection.
Even within the individual tumour, different cancer cell types may exist and over time, these cancer cells may evolve to form newer, often more malignant, cells. They learn to hide; they learn to change; they learn to pump out the drugs we use to target them. What they need to achieve this is time and the great paradox is that as we are all living longer, there is more of an opportunity for cancer to form and develop its strategies. It seems logical, then, that we should think of cancer as something that will require many treatments.
Within this year’s cohort at RebelBio, we have started several new battles in the war against cancer and these companies will fight on different fronts. Interestingly, these companies as well as being ingenious in their individual ways, also, have sought early revenues that are in line with their long term therapeutic developments. This makes them a particularly attractive proposition given that they contain the wherewithal to not just survive, but prosper as business entities on the long road to the ultimate goal.
Cyca Oncosolution
Nusrat Sanghamitra is a chemist by training. A chemist who upon witnessing her own fathers suffering not just due to Cancer, but also the treatment, decided to dedicate herself to find a solution to improve the quality of life of cancer patients. And she did what chemists sometimes do. She made molecules in the form of chemotherapeutic drugs aiming to get a better drug with fewer side effects. And much like other chemotherapeutic drugs, they mostly turned out to be very toxic to even healthy cells. It’s generally an achievement if we can design therapies that we can allow to travel to all parts of the body. It’s even more astonishing if we can get a new molecule directly into the cell. The reason we live at all is that our building bricks know how to regulate what comes in and out via gated channels. This is as true of cells grown in petri dishes as much as it is in the body. The upshot of this is that we tend to have to flush a lot of toxic chemicals into the body so that a tiny amount of it become truly bioavailable.
It’s these doses that can make us very sick indeed. Nusrat, therefore, changed tack and focussed many years of research upon how one could beat the cells security system. The answer arrived in the form of the needle molecule, a revolutionary piece of nature’s structure designed to walk across the normal cell membrane in seconds without itself causing any toxicity or cellular damage. This needle molecule is very exciting development not just for the area of drug delivery but also for all molecular biologists who recognise the value of this magic delivery system. Nicknamed a FedEx for drugs by Nusrat herself, this delivery system has the ability to carry molecules (or drugs) as small as a fluorescent dye or anticancer drug cisplatin to as large as CRISPR-cas9 straight in the cell without the need for high doses. It is a piece of technology that will probably change much of what we currently do in the lab today and has caused a huge stir among members of the scientific community who have turned their eyes towards it.
Valanx
Austrian Scientists Michael Lukesh and Patrick Fleascher spent several years as PhD student at the University of Graz. During that time, they became world experts at the production of non-canonical or novel amino acids. These amino acids can be used to confirm superpowers upon whatever protein they could be inserted into. An obvious use therefore would be the attachment of a chemotherapeutic agent to a tumour specific antibody. This is not an entirely new idea. However, they were prohibitory expensive or it was a regulatory mess because of the non-uniformity of the product produced. And so this therapeutic approach has to this point never really taken off in the way it deserves to. Now Valanx have shown that they can produce these non-canonical amino acids more cost effective and also create a uniform product to satisfy the FDA and other bodies. This game changing advance has huge ramifications for antibody based therapeutics across all diseases. Yields of these amino acids are impressive, orders have been made and their application virtually limitless and the economics impressive to the extent that we will soon see more supercharged antibody therapies entering the drug pipeline.
SwaLife Biotech
Genomic instability is one of the most pervasive characteristics of tumour cells and is probably the combined effect of DNA damage, tumour-specific DNA repair defects, and a failure to stop or stall the cell cycle before the damaged DNA is passed on to daughter cells. Although these processes drive genomic instability and ultimately the disease process. In spite of these, Cancer also needs to be able to repair certain damage to allow itself to survive and it has been demonstrated that the ability of cancer cells to repair therapeutically induced DNA damage impacts therapeutic efficacy. This has led to targeting DNA repair pathways and proteins to develop anti-cancer agents that will increase sensitivity to traditional chemotherapeutics.
SwaLife Biotech was formed by Dr Pravin Badhe and Dr Basudev Paudyal, friends who met in London where both were doing their PhDs. They have discovered five novel alkaloids from plants. Their focus has been on the synthesis of these discovered compounds and they have impressively characterised these compounds for anti cancer properties, particularly effective in treating pathway in skin and breast cancer. A target-specific experiment showed that these novel alkaloids have inhibited DNA damage response (DDR) in skin and breast cancer. Besides, these novel alkaloids, they have generated numbers of plant extracts and fractions rich with phenolic compounds. These phenolic extracts and fractions have shown excellent UV protective effect, anti-inflammatory, anti-oxidant and anti-photo aging properties. This has led them to propose their use in the skin care products formulation to generate revenue to take their long term goal of development of novel small molecule alkaloids to higher valued anti-cancer drug out in the market. They proposed that reinvented skin care product using plant extract would allow us all to tan safely, obtain much needed Vitamin D (which traditional creams block) while truly protecting us from the suns damaging effects. Their first product “Natural midnight sunscreen” is ready and will be in the market soon.
OACP
Back in 2016, an article in Forbes by Alice G Walton highlighted just how waiting upon a result that could be good or bad the can be far more stressful than knowing a bad result. We are simply hardwired to find such uncertainty excruciating.
Enrico Di Oto was working in a testing lab of the University Hospital in Bologna for over 13 years. He estimates that during that time, he carried out perhaps 15000 FISH (Fluorescent In Situ Hybridisation) assays. Considered the gold standard in detecting cancer’s signature gene, it has the disadvantage of taking too long. Usually, an overnight assay is the minimum for the reaction to truly be elucidated. Given that one could several hundred samples in a cue, it usually takes several days between a patients test and the delivery of the test outcome. Apart from the delay in treatment, which could have serious ramifications when dealing with more virulent forms, it is the psychological torture of the wait that Enrico understands well and which forced him and his colleagues to act. While working at the hospital, during his PhD, he carried out research looking more carefully at the components of the FISH and other ISH (in situ hybridisation) assays and started to work on making them faster. The result is OACPs booster solutions which can allow traditional assays to produce a result in two hours. Due to the increased test efficiency, by using OACPs boosters it is also possible to reduce the costs of the tests by 50%, making them more affordable for labs. OACP have already opened up their distributor networks and are selling to across European markets.
These four companies are approaching the war on cancer from different angles. And there is plenty room for more of where they are coming from. Cancer can evolve and for us to win the war, we also need our weapons to evolve faster. Products that can change lives by easing suffering and that will see the wider world in a matter of months, not years. There are a lot of reasons to be motivated to start a company that will deliver therapeutics and treatment for this disease. We believe there are people walking around today whose lives will someday be saved by a company. That’s a big thought and one that makes us justifiably proud.
Originally published at rebelbio.co on July 19, 2017.
