Last time I talked about why treating cancer is so hard:
Briefly, scientists did complete genome sequencing of seven individuals prostate tumors, and things were all kinds of jacked up. Not only were all seven tumors different, but one tumor had over 200 chromosomal rearrangements. Like taking your genome and shuffling it like a deck of cards.
As if that kind of complexity isnt bad enough…
Another group of scientists sequenced the genomes of acute myeloid leukaemia patients pre- and post-treatments:
Turns out some tumors react to chemotherapy the same way bacteria respond to antibiotics and HIV-1 responds to antiretrovirals:
But the HIV-1 monster does not want. HIV-1 operates as a ‘quasispecies’, that is, a large population of genetically distinct, yet related organisms. It turns out that no matter how many lazrs scientists pointed at the HIV-1 quasispecies… they could not kill all of them! Just by chance, the quasispecies contains variants that are resistant to every lazr. Luckily, these variants are less fit than a wild-type virus– ‘resistance’ comes at a fitness cost. HAART keeps viral loads low because its harder for the drug resistant viruses still alive to reproduce.
But the HIV-1 monster DO NOT WANT! Slowly, but surely, these less-fit resistant variants start accumulating secondary compensatory mutations, which create viruses that are resistant to teh lazrs, but ALSO are extraordinarily fit. This is when HAART fails, and the patient needs to switch drugs.
Because of the genomic diversity of the population of tumor/bacteria/virus, when you apply the treatment, there is a small sub-population that is resistant to the treatment. That small sub-population replicates (+ the associated mutations) selecting for increases in replication capacity in the presence of the drug.
The cancer cells grew in number, and as they did, they accumulated a lot of mutations, some of which are listed in the figure next to the star. All of these mutations, one after the other, took over the entire population of cells-a signature of natural selection. When the woman went to her doctor, however, the cancer had diversified into a number of different lineage, each carrying additional, distinctive mutations. Over half of the cells belonged to a lineage marked here in purple, known as cluster 2. Cluster 3, marked in yellow, was made up cells with a separate set mutations. And from within Cluster 3 emerged yet another lineage-Cluster 4, marked in orange. The dots in each circle show the sets of mutations that accumulated in each cluster.
The chemotherapy knocked down all the clusters of cancer cells to such low numbers that doctors couldn’t find them any more. But they were still there. And when exposed to chemotherapy drugs, the most successful cluster was not the one that had been most successful back when the cancer was diagnosed. It was the relatively rare Cluster 4. Apparently, it had mutations that made it better able to withstand the chemotherapy drugs. Some its descendants later picked up new mutations, which enabled them to reproduce quickly and take over the cancer population, as they resisted new chemotherapy drugs as well.
These are just long ways of saying: Evolution–>drug resistant tumors.
Another reason why treating cancer is so damn hard.