5 ms·

Why are all the gene-based cancer breakthroughs I've seen in the news for blood diseases? Is it easier to manipulate genes in blood?

by mchahn 11y ago

teekert 11y ago
I think it is because in blood drugs and gene based treatments are the only option, surgery is simply not an option. This has always spurred the blood cancer field to take greater risks, the all or nothing approach.
- erkkie 11y ago
  Surgery is an option, namely bone-marrow transplants. The reason blood cancers are first with these techniques boils down to having better known antigen targets to target compared to solid tumors where known antigens have more cross reactivity to other tissues (so less specificity, more side-effects).
  - carbocation 11y ago
    Despite the word "transplant", bone marrow transplants are not done surgically; they are done by infusion of donor cells into the bloodstream. Then, the cells seek out their own niche and engraft.
    - erkkie 11y ago
      Good point, you're right, not surgery, more like an (significantly invasive) procedure. Still good to differentiate from "giving a drug".
- pacap 11y ago
  From what I remember, these blood cancer have an antigen, CD13 or something, which is unique to them - no other body part has it, making it easy to target them. Otherwise, you get the side effect of destroying your own body, the case of a woman a few years ago, who died having her lungs destroyed by immunotherapy. Lungs had the same antigen. This morning I read something hopeful in this direction - UCSF researchers designed an AND gate, so now they could trigger a T cell attack only when 2 specific antigens are present, making it much more reliable. And I could imagine these can be chained, further narrowing it down. It needs genetic sequencing to isolate. https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-cells-could-attack-cancer-spare-healthy-cells https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-... At the moment this is a terrible manual and time consuming process, so it is expensive.
  - erkkie 11y ago
    This is also why a combination of engineered T-cells and immune checkpoint inhibitors is a really winning combo. http://www.theguardian.com/society/2015/jun/01/paradigm-shift-hailed-in-treatment-of-lung-cancer http://www.theguardian.com/society/2015/jun/01/paradigm-shif...
    - AstralStorm 11y ago
      Immune checkpoint (fancy name that, you probably mean anti-autoimmune system) inhibitors main problem is the very high risk of autoimmune disorders that are hard or impossible to treat. Just toggling the suppressor will not kill clonal cells already in circulation, and those can last a long, long time, or even a lifetime. If you're unlucky, you will also get "broken" immune memory cells - which also last for life. Trading cancer for SLE or rheumatoidal arthritis etc.
forgotpwagain 11y ago
In general, blood cancers are more accessible than solid tumors. With blood cancers, the majority of the cancer cells are in the blood or in very well perfused tissues (bone marrow, spleen, thymus, etc), meaning that drugs/treatments can get to the targets very easily. With solid tumors, you have to deal with the complexities of the tumor microenvironment. The tumor microenvironment is the complex environment of the cancer tumor tissue. Of particular note, decreased lymphatic drainage, increased connective tissue, and aberrant angiogenesis (growth of new blood vessels) create very high interstitial fluid pressures within the tumor, limiting the ability of drugs or cells to penetrate within the tumor and "work their magic" by reaching the cells/target molecules of interest, etc. Blood cancers are a good proof-of-principle for many cancer therapies; translation to solid tumors is difficult (see challenges with CAR-T cell immunotherapy). As for gene manipulation in blood--yes, it is relatively easy to manipulate genes in blood. Hematopoetic Stem Cells (which differentiate into all different kinds of blood cells) can be withdrawn without too much difficulty, manipulated in the lab, and then reinjected into the patient.
- agumonkey 11y ago
  Pardon the naive question, I don't know how localized therapies are today, but hasn't there been research into developing fake foreign capillaries to be implanted non invasively to deliver drugs right on target ? ps: I remember seeing more 'barbaric' version of the idea, namely metal pipes planted in the patient as a direct path. I was wondering about something more organic.
  - forgotpwagain 11y ago
    I'm not an expert, but I think there's been a variety of attempts for vascular renormalization--to restore the normal flow of vessels to allow for drug delivery, etc. Rakesh Jain's lab (at MGH) is a big player in this field and is worth looking up if you're interested. I'm not personally familiar with work in developing capillary devices, but it wouldn't surprise me at all if this was an approach under development--it certainly makes a lot of sense.
    - 11y ago

Why are all the gene-based cancer breakthroughs I've seen in the news for blood diseases? Is it easier to manipulate genes in blood?

by mchahn 11y ago

Why are all the gene-based cancer breakthroughs I've seen in the news for blood diseases? Is it easier to manipulate genes in blood?

teekert 11y ago

I think it is because in blood drugs and gene based treatments are the only option, surgery is simply not an option. This has always spurred the blood cancer field to take greater risks, the all or nothing approach.

erkkie 11y ago
Surgery is an option, namely bone-marrow transplants. The reason blood cancers are first with these techniques boils down to having better known antigen targets to target compared to solid tumors where known antigens have more cross reactivity to other tissues (so less specificity, more side-effects).
- carbocation 11y ago
  Despite the word "transplant", bone marrow transplants are not done surgically; they are done by infusion of donor cells into the bloodstream. Then, the cells seek out their own niche and engraft.
  - erkkie 11y ago
    Good point, you're right, not surgery, more like an (significantly invasive) procedure. Still good to differentiate from "giving a drug".
pacap 11y ago
From what I remember, these blood cancer have an antigen, CD13 or something, which is unique to them - no other body part has it, making it easy to target them. Otherwise, you get the side effect of destroying your own body, the case of a woman a few years ago, who died having her lungs destroyed by immunotherapy. Lungs had the same antigen. This morning I read something hopeful in this direction - UCSF researchers designed an AND gate, so now they could trigger a T cell attack only when 2 specific antigens are present, making it much more reliable. And I could imagine these can be chained, further narrowing it down. It needs genetic sequencing to isolate. https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-cells-could-attack-cancer-spare-healthy-cells https://www.ucsf.edu/news/2016/01/401471/tricked-out-immune-... At the moment this is a terrible manual and time consuming process, so it is expensive.
- erkkie 11y ago
  This is also why a combination of engineered T-cells and immune checkpoint inhibitors is a really winning combo. http://www.theguardian.com/society/2015/jun/01/paradigm-shift-hailed-in-treatment-of-lung-cancer http://www.theguardian.com/society/2015/jun/01/paradigm-shif...
  - AstralStorm 11y ago
    Immune checkpoint (fancy name that, you probably mean anti-autoimmune system) inhibitors main problem is the very high risk of autoimmune disorders that are hard or impossible to treat. Just toggling the suppressor will not kill clonal cells already in circulation, and those can last a long, long time, or even a lifetime. If you're unlucky, you will also get "broken" immune memory cells - which also last for life. Trading cancer for SLE or rheumatoidal arthritis etc.

forgotpwagain 11y ago

In general, blood cancers are more accessible than solid tumors. With blood cancers, the majority of the cancer cells are in the blood or in very well perfused tissues (bone marrow, spleen, thymus, etc), meaning that drugs/treatments can get to the targets very easily. With solid tumors, you have to deal with the complexities of the tumor microenvironment. The tumor microenvironment is the complex environment of the cancer tumor tissue. Of particular note, decreased lymphatic drainage, increased connective tissue, and aberrant angiogenesis (growth of new blood vessels) create very high interstitial fluid pressures within the tumor, limiting the ability of drugs or cells to penetrate within the tumor and "work their magic" by reaching the cells/target molecules of interest, etc. Blood cancers are a good proof-of-principle for many cancer therapies; translation to solid tumors is difficult (see challenges with CAR-T cell immunotherapy). As for gene manipulation in blood--yes, it is relatively easy to manipulate genes in blood. Hematopoetic Stem Cells (which differentiate into all different kinds of blood cells) can be withdrawn without too much difficulty, manipulated in the lab, and then reinjected into the patient.

agumonkey 11y ago
Pardon the naive question, I don't know how localized therapies are today, but hasn't there been research into developing fake foreign capillaries to be implanted non invasively to deliver drugs right on target ? ps: I remember seeing more 'barbaric' version of the idea, namely metal pipes planted in the patient as a direct path. I was wondering about something more organic.
- forgotpwagain 11y ago
  I'm not an expert, but I think there's been a variety of attempts for vascular renormalization--to restore the normal flow of vessels to allow for drug delivery, etc. Rakesh Jain's lab (at MGH) is a big player in this field and is worth looking up if you're interested. I'm not personally familiar with work in developing capillary devices, but it wouldn't surprise me at all if this was an approach under development--it certainly makes a lot of sense.
  - 11y ago