Life is possible through many different biological pathways.
Cells alone have such complicated signaling cascades that researchers are
finding new proteins and new interactions with old proteins constantly. Cancerous
cells come about when those pathways are manipulated or mutated to promote cell
growth and replication while inhibiting cell death. This
article is a foundational review of some of the pathways cancers take
advantage of. To summarize the article pathways start at the cell
membrane/surface and are relayed until the signal can control gene expression
in the nucleus. A couple of pathways the article touches on include the
Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways. Within these two pathways
of cell growth/replication the cell has ways to inhibit the growth/replication
by turning to self destruction/apoptosis. However, cancerous cells have
mutations in those negative feedbacks. It was recently found that both of these
pathways co-regulate many downstream targets involved in growth/replication
regulation at the same time. Thusly, these two pathways must be inhibited at
the same time to effectively stop cancerous growth. Drugs that inhibit mTOR
production alone were thought to be promising at first until further studies
found the inhibition to be counterproductive. When mTOR, which is produced by
the activated Akt, is inhibited it turns on a secondary Akt activator to
promote further Akt production and therefore further mTOR production. In
essence the cell has a switch to reactivate mTOR through overproduction of Akt.
The only sure thing was finding a way to inhibit mTOR, PI3K, and the secondary
Akt activator. Classical chemotherapies tend to target systems much further
down the cascade than these signals, such as actual DNA replication or cell
division, and in doing so increase a cell’s tendency to move towards cancerous
behavior by activating cell survivor mode pathways which trigger the two
pathways mentioned above. The next exciting step in cancer treatment very well
may be creating a single drug that can inhibit both of these pathways
effectively and minimize toxicity. I will follow up with more recent
publications.
