Alright, to review where we've been with this series of 5 talks about the biology of cancer.
So how a good cell goes bad? You have DNA damage because of environmental or other
reasons and hopefully that repairs. But if it doesn't repair, that failure of DNA repair
because either the mechanisms to repair are abnormal or we just have so much damage
that we can't actually repair it, we have mutations in the genome of somatic cells. That
mutation will lead to the activation of growth promoting oncogenes or the inactivation of
tumor suppressor genes or alterations in genes that regulate apoptosis. We'll get
unregulated cell proliferation and decreased cell death which will give us a clonal expansion.
In the next series of talk, we are going to revisit these additional topics; angiogenesis,
a escape from immunity, tumor progression, malignant neoplasm, all the things that will
eventually get us to invasion and metastasis. So that's the next series. Just as big picture
points in biology and when we think about cancer, cancer is fundamentally a genetic disease.
It happens because of non-lethal genetic damage. If the genetic damage and the breaks
and all those errors were lethal, the cells would kill themselves. So this means it's just the
right amount of genetic mutation without having the capacity to be lethal. There are 6
general classes of genes that we need to think about that are involved when we're talking
about malignancy. One are the oncogenes. So these are going to be the accelerator. If we
have too much acceleration, then we're going to have too much growth. Loss of tumor
suppressor genes. So we've taken our foot off the break, we don't have enough breaking
so we can't inhibit the process. And remember those are things like p53 and RB. The DNA
repair genes. So those are going to be very important in terms of preventing mutations
that occur when we have genetic damage. We want to have to feel safe. If cells are so bad,
we want them to kill themselves rather than to continue to grow and so in cancer loss
of apoptotic genes such as overexpression of BCL2 or loss of BAX and BAK are going to lead
to increased cellular proliferation, uncontrolled. The telomerase gene needs to be
reactivated to prevent replicative senescence. And finally, micro RNAs depending on
whether they are acting on proto-oncogenes or they're acting on tumor suppressor genes
or whatever can have all the effects of the other 5 bullet points. Final big picture concepts.
There is a clonal expansion of some damaged precursor cell. Many of the pathways that are
shown above will be affected. It is a multistep process in most cases. There are exceptions
where a single driver mutation is enough to drive malignancy, but that tends to be the
exception rather than the rule. Within any given tumor, bullet point number 2, there is
significant heterogeneity. It is not a uniform mass of cells and whether some of those cells
have metastatic potential or some of those cells have inability to grow with less amount
of growth factors or whether some of those cells have stem-like properties, it is a basically
heterogenous population of cells. And then cancer stem cells are an important concept
regardless of how they may be derived because they can initiate and sustain the tumor.
And with that, we've covered a lot of oncology. If you got this, you understand cancer
really really well.