BETA - What is conventional therapy? What anti-myeloma treatments are considered conventional chemotherapy?

So conventional chemotherapy is therapy that targets more proliferative shells. Cancer cells by definition are going to be more proliferative than traditional cells in our bodies. Melphalin, which a lot of patients will get as part of their autologous stem cell transplant, other drugs like cyclophosphamide or cytoxin, a similar agent, target rapidly proliferating cells which again myeloma cells are, but we also have some cells in our bodies at baseline that are rapidly proliferating. So these kinds of agents have a little more side effects. You may see some GI side effects, you may see some loss of energy, loss of appetite, things like that are often times associated with conventional chemotherapies. So immunotherapy is a relatively new field in cancer therapy where we're targeting our immune system to help control the cancers, to basically look at cancer cells as if they are bacteria or they're viruses and take advantage of our immune system to eradicate them much the same way that they should eradicate things like bacteria or viruses. So there's lots of agents that we're using in myeloma now that would be immunotherapies. So things like IMIDs like the thalidomide, linalidomide, pomalidomide, these are agents that actually while they do have some direct effect on the myeloma cells, the majority of their effect are actually on the environment that supports the myeloma cells and targets them to actually not support the myeloma cells as well. Some of the monoclonal antibodies work in a similar fashion as well. Certainly some of the newer therapies like the CAR-T therapies where we re-engineer someone's immune cells to actively attack the myeloma cells are definitely immunotherapies. This is a really exciting new frontier for myeloma therapy and the early results are quite positive. The conventional chemotherapy is going to predominantly attack the rapidly dividing cells which will attack the myeloma cells but will also have more off-target effects. The immunotherapy are not really going to attack the myeloma cells, it's going to supercharge our body to attack the myeloma cells. Some of the off-target effects you can get with that are going to behave like you have a bad infection or a bad cold because you're tricking your body into thinking that you do sometimes so those can have those kinds of side effects but you shouldn't have the side effects that you would typically see with the conventional chemotherapy, the things like the GI side effects and sometimes loss of hair and things like that. So targeted therapies are therapies that target specifically cancer cells, specifically in our case myeloma cells. A good example of a targeted therapy in myeloma would be the proteasome inhibitors which take advantage of cells that are actively making lots of proteins and fortunately can't recycle the byproducts of protein synthesis and by inhibiting that, that allows us to target specifically those cells that are making lots of proteins which myeloma cells do and that selectively kills the myeloma cells and leaves most other cells relatively untouched. So in classical chemotherapy you're going to have a lot more off-target effects because in classical chemotherapy you're treating just more proliferative cells. While myeloma cells are more proliferative, there are also other cells in our body that are more proliferative at baseline so by using conventional chemotherapy those cells are going to be affected. The targeted therapies are a lot more specific to the myeloma cells and that should have less off-target effects, less side effects from the agents. This is a really interesting subject and a little bit somewhat controversial as to what therapies are considered classical chemotherapy and what are targeted therapies. Some people use the term chemotherapy broadly to encompass any type of treatment that's used for cancer and this can include drugs that we would call classical chemotherapy as well as our targeted therapies as some people believe this term refers to all of them combined. That being said, the term chemotherapy or classical chemotherapy really refers to agents that were mostly developed around and just after World War II that were developed a generation ago to treat a variety of different cancers and they were really developed with the thought in mind of how do we attack cancer cells and cancer cells are cells that often divide rapidly and without following the cues of our body to tell them to stop. This is why classical chemotherapy agents tend to make people unfortunately throw up and have their hair fall out because the cells that line our GI tract and our hair tend to grow rapidly. Chemotherapy drugs from that generation interfere with those processes for all cells. That being said, we now have a new generation of what we call novel therapies and novel or targeted therapies are agents that really focus more on the cancer cells themselves so they have better efficacy because they don't spend time on non-cancer cells as much and they have a better toxicity profile because they don't affect those other cells. So nowadays we refer to the novel therapies such as drugs like monoclonal antibodies or proteasome inhibitors as drugs that are novel as in a new generation from what we call the classical chemotherapy agents. So targeted therapies are going to act more directly on the cell itself whereas immunotherapies are going to work more on the cells that help to either support the myeloma cells that are unfortunately helping the myeloma cells proliferate or they're going to help supercharge our immune system to attack the myeloma cells but in general immunotherapies do not actively attack the myeloma itself. They either attack the supportive cells or they supercharge our body to help attack the myeloma. So combination therapy is really the core of myeloma therapy. Using a single agent or a single class of agents is helpful to an extent but often times is only minimally helpful for longer periods of time. By using multiple classes of agents in combination is when we really start to see the deeper and the more durable or longer term remissions and benefits for our myeloma patients. So the HDAC inhibitor, Panabinostat, is the only agent that's approved in this class for myeloma. So Panabinostat is a histone deacetylase inhibitor, an HDAC inhibitor and HDACs, well histones are actually the sort of the molecule that DNA wraps itself around to be stored and the way that DNA is able to replicate and to start the process of cellular division is by unwinding from these histones, these cores that they're wound around and that's done through a process called acetylation and when you inhibit that, when you inhibit the ability for those proteins to be unwound and then rewound around that, that has significant effects in the body's ability to continue to have these cells divide and to proliferate the way that they normally would. The myeloma cells are more proliferative and they take advantage of these histone acetylases and histone deacetylases so when you inhibit the histone deacetylase it does not allow that unwinding and rewinding process to happen appropriately and that does lead to cellular death. There are a little bit more off target effects with this because there's other cells in our body that do have this, that do use this process as well but not as much as the myeloma cells so this would be more of a, it's a targeted therapy but it does have more off target effects, not quite as much as conventional chemotherapy. So selective inhibitors of nuclear exportin or SINES are agents that interfere with a shuttling protein that shuttles proteins from the nucleus out into the cytoplasm and some of these actually have significant effects when they're stuck in the nucleus. Most often we're talking about tumor suppressors and when these tumor suppressors are shuttled into the cytoplasm they're no longer beneficial but when they're in the nucleus they are still beneficial so myeloma cells often times are able to shuttle these good proteins out of the nucleus into the cytoplasm where they don't really have an effect so by inhibiting that, inhibiting the chaperone protein that shuttles them out you get increased buildup within the nucleus which in and of itself can kill the cells but also the beneficial effects makes those proteins have their effect in the nucleus where it's supposed to be. This would be more of a targeted therapy because this is something that while it's present in other cells is predominantly present in hematologic malignancies. There's uses in other types of cancers besides just myeloma but predominantly in hematologic malignancies. How are we able to use targeted therapies when patients have so many different mutations and every patient's a little bit different and that is true and that does make it more challenging so that's why we look for some of these more ubiquitous mutations and ubiquitous changes that are specific to the myeloma cells. I love to get to an area to a time when we can actually have such personalized therapies that we're able to actually target everyone's specific mutation load. One of the real exciting parts of immunotherapy is that the more different a cancer cell looks from a normal cell, from the cell that its origin was so a lung cancer cell that has now transformed into a lung cancer cell, the more different that looks the more likely those cells are to respond to classic immunotherapy because it's easier for the body to recognize that cell as being very abnormal. The cells that are only mildly abnormal are not as susceptible to immunotherapies but that's sort of looking at globally just sort of supercharging our immune system to attack cells that are somewhat odd or abnormal. If we can get to a point where little mutations that every patient has are targetable that would be ideal. We're still a ways away from that. Quite honestly I think that the infrastructure to do something like that is pretty significant and I don't know that that exists right now.