Side Effects of Chemotherapy: Overview

00:02 Welcome back.

00:04 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.

00:14 There is no free lunch, as the saying goes in cancer therapy.

00:20 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.

00:35 The goal is to actually have much more targeted therapy that with surgical precision, kill just cancer cells and not normal cells.

00:43 We are not there yet, with rare exception.

00:46 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.

01:00 But that's the exception rather than the rule.

01:02 And so their consequence of having cancer and the treatment of cancer is that there can be a variety of pathologies associated.

01:10 So we're going to briefly cover some of those, since you're aware and thinking of that.

01:14 Here's where we are on our roadmap and we're at the final block- Effects of therapy.

01:20 So there are side effects of therapy.

01:24 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.

01:33 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.

01:50 Chemotherapy is going to act not only on rapidly proliferating tumor cells, but labile cells.

01:57 In say, the bone marrow that are constantly turning over to make new marrow elements so you can get neutropenia and a secondary infection.

02:04 You can get thrombocytopenia and have a bleeding disorder.

02:08 You can have a variety of effects that are causing an anemia.

02:13 So chemotherapy is not totally benign.

02:16 And actually, we can also have neutropenia and infections that occur before therapy too because the tumor may in some cases be immunosuppressive.

02:25 But chemotherapy is going to make those that much, much, much worse.

02:30 Chemotherapy, again, is not a directed toxin.

02:35 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.

02:57 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.

03:19 However, that same effect causing DNA breaks or causing abnormal insertion of certain nucleotides can cause secondary malignancies.

03:31 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.

03:55 Yikes.

03:57 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.

04:13 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.

04:23 The arm on that side will not be able to drain fluid and will become massively edematous.

04:29 There are secondary consequences of that including malignancy but it's also disfiguring and can lead to loss of function.

04:40 Radiation, so one of the tools and our armamentarium that allow us to go after cancers are radiation.

04:48 But we can't in many cases, get the radiation just into the tumor, we have to shoot from the outside.

04:54 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.

05:06 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.

05:20 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.

05:28 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.

05:42 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.

05:54 And finally, there's immunotherapy.

05:55 So we're getting to the point where we can use inhibitors of the pathways that would normally suppress the immune response.

06:04 Cancers are very clever and they can suppress the immune response by expressing certain molecules.

06:10 For example, Programmed death ligand-1.

06:14 Well, we now have antibodies that block that.

06:17 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.

06:34 So let's look at these each in turn.