By Roy de SouzaBig pharma companies are investing in oncology drug discovery. Unfortunately for patients and for pharma companies, such a drug will probably never exist. Because cancer in two different patients is almost always different, different drugs will be required for both patients.
To understand why we need to look at the actual cancer cells. We need to see if cancer cells in two patients are the same or different. Sophisticated sequencing equipment from companies like Illumina (a $50bn market cap company led by NRI Francis de Souza) and Thermo Fisher allow us to see the DNA of each patient’s cancer cells. Cancer is mutated human cells that grow very fast. And by mutated cells we mean that some of the genes, some of the 20,000 genes in each cell, have gone wrong.
There are two key types of mutations
Trunk Mutations
Certain genes define your hair color. Other genes define your eye color. Similarly certain genes decide when cells should grow. When these “growth genes” go wrong (mutate), we call them trunk mutations like the trunk of a tree. Trunk mutations start the cancer. Trunk mutations make otherwise normal cells grow and grow and grow. Then a tree of new mutations forms above the trunk.
Branch Mutations
Because of the rapid uncontrolled growth caused by a trunk mutation, more mutations start appearing. These mutations are called branch mutations and are pictured as branches growing from the trunk of a tree. Some branches get two new mutations and so split into two sub-branches.
Each mutated gene creates a different problem. One mutation in one patient may cause the cancer cell to create VEGFA, which triggers more blood vessel growth and supplies more glucose to growing cells.A mutation in the second patient may cause the cancer to create too much PGE2 which harms dendritic cells and T-cells. Pharma companies can develop an anti-VEGF drug to solve the problem created by the mutation in the first patient. Genentech (Roche) has done that and it’s called Avastin. But the mutation in the second patient causes a completely different problem. To solve it pharma needs to develop a PGE2 inhibitor. Clearly the same drug for both patients won’t work: they have different problems and need different drugs.
Even in one patient, say P210, each of the mutations is causing different problems, so each branch may need a different drug to treat it. That means that a combination of 3-10 drugs may be required for just one patient. And a different drug to treat every single probably doesn’t exist.
For patient P45 a different drug or combination of drugs will be needed. This patient has a trunk with 6 mutations. If we can treat one of these 6 we may just be lucky and kill all cancer cells because all cancer cells have the trunk mutations. However one of the branch mutations may create something that protects the cells from this drug. If so one drug won’t work for this patient. And again this patient P45 clearly needs different drugs from patient P210.
So the way for pharma companies to cure all cancer will not be to invest billions of dollars looking for super drugs that works for all or most patients. Instead we will need a combination of drugs. We will need personalized medicine: a different combination of drugs for each patient that matches the mutations their cancer cells have. One way to build such a combination is to build many types of T- cells – each type of T-cell to target one mutation. This strategy is called a Personalized neoantigen vaccine or a Personalized cancer vaccine. It’s clever, but even that won’t be enough. However, by adding other drugs to a Personalized Neoantigen Vaccine we could get it to work in some patients.
So one drug to kill all cancer cells will never be discovered. But great scientists know this and are working hard. Software to analyze one patient’s cancer cells, then design a combination treatment and then manufacture just enough for that one patient, could work. This is the dawn of personalized medicine.
(The author, Roy de Souza is a technology entrepreneur. When a family member was diagnosed, he moved his focus to curing difficult metastatic cancers for the sake of patients and their families. He leveraged his cloud software experience into personalized medicine which designs a new drug for each cancer patient. He has a Masters from Oxford and an MBA from The Kellogg School.)