We're going to be into the final
stages of our discussion about cancer
and talk about the effects that
happen because we treat cancer.
There is no free lunch, as the
saying goes in cancer therapy.
There is a lot of collateral damage because
what we're basically doing is dumping in
toxins and/or radiating tumors
to try to eliminate them
but we are also going to be damaging
normal tissue in the process.
The goal is to actually have much more
targeted therapy that with surgical precision,
kill just cancer cells and not normal cells.
We are not there yet, with rare exception.
So there are some new, newer drugs, such as
the BCR-ABL inhibitors, a Gleevec - Imatinib
that can specifically target the kinase
that's being elaborated by the tumor.
But that's the exception rather than the rule.
And so their consequence of having
cancer and the treatment of cancer
is that there can be a variety
of pathologies associated.
So we're going to briefly cover some of those,
since you're aware and thinking of that.
Here's where we are on our roadmap and we're
at the final block- Effects of therapy.
So there are side effects of therapy.
In chemotherapy, we can get a tumor lysis
syndrome, we'll talk more about that
but if you have a massive tumor burden, and
then you kill those cells, yay, good thing.
except, there are lots of compounds,
molecules, enzymes and ions
within that tumor that you've
killed that you release as a flood
into the vasculature and that can have consequences.
Chemotherapy is going to act not only on rapidly
proliferating tumor cells, but labile cells.
In say, the bone marrow that are constantly
turning over to make new marrow elements
so you can get neutropenia and a secondary infection.
You can get thrombocytopenia
and have a bleeding disorder.
You can have a variety of effects
that are causing an anemia.
So chemotherapy is not totally benign.
And actually, we can also have neutropenia
and infections that occur before therapy too
because the tumor may in some
cases be immunosuppressive.
But chemotherapy is going to make
those that much, much, much worse.
Chemotherapy, again, is not a directed toxin.
For the most part, it is a toxin that will
affect every other normal tissue to some extent
And that's the trade off that we
currently have with the state of the art,
that we expect that many of our toxins
that were giving us chemotherapy
will also have some degree of liver toxicity,
kidney toxicity, lung toxicity, GI and heart.
And in many cases with chemotherapy,
some of the chemotherapy is designed
to specifically cause DNA breakage and cause
damage that the tumor cells cannot correct
before they try to go through a
mitosis and therefore, they die.
However, that same effect causing DNA breaks or
causing abnormal insertion of certain nucleotides
can cause secondary malignancies.
So a non-uncommon scenario is a young child who
has non-Hodgkin's lymphoma or Hodgkin's disease
or has leukemia and gets treated with
chemotherapy and then 20 years later,
presents with another new tumor
unrelated to that previous tumor
but is caused by the mutations
we induced with our chemotherapy.
Lymphedema, so when we do surgery, the
surgeons are awesome in carving out the tumor,
They also will often take associated lymph
nodes, and then when we take the lymph nodes,
we don't have appropriate drainage
of fluid out of the say, affected limb.
And a common scenario is in a breast
cancer patient who gets a mastectomy
and a lymph node dissection, sometimes
associated with radiation as well.
The arm on that side will not be able to drain
fluid and will become massively edematous.
There are secondary consequences
of that including malignancy
but it's also disfiguring and
can lead to loss of function.
Radiation, so one of the tools and our armamentarium
that allow us to go after cancers are radiation.
But we can't in many cases, get
the radiation just into the tumor,
we have to shoot from the outside.
And let's say that there is a tumor in the
lung, I'm shooting through to get that tumor
but there happens to be a heart,
kind of in the middle of that
which is potentially subject then to damage.
There are exceptions, so if we are
trying to radiate a prostate tumor,
we may actually put in radiation
beads that can be specifically
targeted into the tumor within the prostate.
But if we do exogenous beam radiation, that's
going to damage the bladder and the rectum
and everything else that happens to be in that area.
And the way that radiation is used or the reason
that radiation is used to treat malignancy
is to induce double stranded
breaks that the tumor cannot repair
as it goes through its normal cell cycle.
And that's how we kill but if we have that
same radiation hitting normal structures,
we can induce secondary malignancies,
much like chemotherapy can
induce secondary malignancies.
And finally, there's immunotherapy.
So we're getting to the point
where we can use inhibitors of the
pathways that would normally
suppress the immune response.
Cancers are very clever and they can suppress the
immune response by expressing certain molecules.
For example, Programmed death ligand-1.
Well, we now have antibodies that block that.
But unfortunately, when we add
those antibodies,we're also
taking the break off the
immune response anywhere else,
and we frequently see secondary autoimmune
phenomena due to the recognition of self antigens
by the host that's being treated.
So let's look at these each in turn.