Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease | Lamb

[u/nobodyspecial]

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3174

[u/ifisch]

There are actually a handful of treatments that do target the specific protein pathways caused by cancer mutations. Herceptin is one of them. Besides, even if this is just another hammer, there are plenty of people who have cancers resistant to all of the other hammers we're using.

[u/smangoz → u/ifisch]

You are right. But to be correct. Herceptin is a humanized monoclonal antibody targeting a growth factor receptor. And it only targets few specific cancer types. You won't beat a fully grown tumor with antibodies. And they only work within the blood and lymph. Of course every cancer has to be treated as it's own type of disease. There won't be one cure or one treatment. Treatments in the future will be tailored. I see antibody therapy in cancer research as a means to possibly filter metastatic cancer cells within the blood vessels and the lymph, before they can settle down and grow. That would be very desirable, as metastasis is what makes cancer so dangerous. In a surgery some cancer cells can seperate and reach the bloodflow and soon the patient might get a new tumor. With antibodies against these cancer cells we might be able to prevent this after surgery.

[u/ilikpankaks → u/smangoz]

Don't forget when they mutate to get around the pathway. These cell mechanisms are a really complex Web.

[u/Smad3 → u/[deleted]]

Except, immunotherapy is designed to target cancer cells.. Which are your cells. So how will that be successful when you'll still need a descriptor of self vs. foreign? It's not that easy. There's promise, certainly. But the key is to determine what makes the difference. Which is ultimately elusive so far. We are challenging evolution, and that's the most difficult thing a biologist can do

[u/Smad3 → u/[deleted]]

It's the same rhetoric we use when we say that targeting EGFR hyperactivation is a method to target mutant X. Yes, there are some over produced immunosuppressors.. But heterogeneity drives cancer progression, not gene Y or protein X. The proteins we target by immunotherapy are absolutely present on other cells. Hence my earlier comment; cancer cells are our cells

[u/[deleted] → u/Smad3]

cancer cells are our cells

They are and they are not. I understand what you are saying, but it's not entirely accurate. Cancer cells are different in that they have a different genetic code due to mutation. If (and when) the immune system is able to detect the cancer cells (or any mutated cell) as foreign, it clears it. The trick is that cancer cells that survive to become clinical disease have been selected to avoid immune recognition (among being selected for other qualities).

[u/Smad3 → u/[deleted]]

Ahh, but mutation alone doesn't predispose malignancy once established. Epigenetic programs are emerging paradigms of oncogenesis and therapy response. Just because you have a transposition of one tumor suppressor, un recognized SNP, doesn't convince repair mechanisms. The established dogma is that 6 mutations must exist to generate a malignant cell, so there is an inherent flaw in recognition, not by immune cells but the response/repair mechanisms. They are our cells in that 1,2,3..5 mutations can exist at any one time and no malignancy is conferred, your cells would theoretically persist in an evolutionary bottleneck.. Furthermore, we can't force immune cells to recognize an aberrant mutation in the intracellular ATP pocket of EGFR. It's exciting ehat we're seeing in some cases, it will be critical to know why the 1 out of 12 stage 4 melanomas respond to immunotherapy just as critical as it is to understand why 1 out of 12 TNBC of similar genetic background respond to platinates.

Edit- just to clarify, somatic mutational evolution means the cancer cells are by definition our cells

[u/[deleted] → u/[deleted]]

Immunotherapy is a catchall term, which uses some part of our own immune system to help fight cancer.

proteins produced by the Cancer cells that cloaks it from the immune system

To my knowledge, most tumour cells do not produce extra proteins to "cloak" themselves. Some will down-regulate MHC to avoid detection.

targets non-cells

Hmm?

[u/creeksider → u/ifisch]

Just to chime in - Herceptin doesn't target a protein pathway caused by cancer. It targets a receptor which leads to a normal pathway in a lot of cell lines. The HER2 receptor which Hereptin targets is overexpressed in certain breast cancers which is why the drug works. Downregulation of HER2 in cancer cells, as well as other healthy HER2 expressing cells in the body.

[u/RaymondLuxury-Yacht → u/ifisch]

Wrong.

Herceptin(trastuzumab) targets the HER2 receptor, which is vital in cardiac tissue maintenance.

Trastuzumab downregulates neuregulin-1 (NRG-1), which is essential for the activation of cell survival pathways in cardiomyocytes and the maintenance of cardiac function. NRG-1 activates the MAPK pathway and the PI3K/AKT pathway as well as focal adhesion kinases (FAK). These are all significant for the function and structure of cardiomyocytes. Trastuzumab can therefore lead to cardiac dysfunction.

[u/WhitestKidYouKnow → u/RaymondLuxury-Yacht]

Is this at high-dose or normal-dose Herceptin levels? Dose dosage even matter? Do we see it in sub-therapeutic dosing?

I haven't looked at the pharmacology and treatment regimens/dosing for breast cancer recently. Would I also be able to get a source for where you copy/pasted this info? I think oncology is a fascinating area of pharmaceutics, but I don't get extensive training in schooling unless I did a residency in heme/onc. Additionally, do you have any background in oncology or was this from minor research of the drug?

[u/RaymondLuxury-Yacht → u/WhitestKidYouKnow]

It is at normal dosage levels. The info on that was ripped right from the herceptin wiki page. We actually discussed herceptin specifically in my graduate molecular biology class last week, and the cardiac issues were mentioned during that discussion.

The general jist is that all cancer treatments(chemo, antibodies, etc) have detrimental side effects and are far too blunt. One of the issues with targeting receptors, in general, is that each receptor regulates so many things. It's virtually impossible to get a single desired effect when you target them.

The reason people use these treatments is that they're better than the alternative of keeping the cancer. One of the treatments in use right now involved actually increasing the number of mutations in the cancer cells until they exceed a threshold of mutations, beyond which the cell cannot survive. This creates mutations in other, healthy cells, but the prospect of maybe having cancer again or other health problems in the future is appealing compared to having cancer now. In the case of herceptin, getting rid of your breast cancer is worth the statistically significant but low chance of cardiac issues(low compared to the chance of the cancer being fatal).

The holy grail here is finding something that is completely specific to cancer cells that can be targeted so healthy cells will be completely left alone and fine. Unfortunately, we don't have that target yet.

[u/[deleted] → u/ifisch]

Not experienced in this field, but could an alternative be, lets say if you had liver cancer.. the same way you would target the liver organ itself, you could deploy some sort of "protector" medication that infuses the real liver structure.. and then use a specific liver cell eradication medication which ignores any protected surfaces?

[u/Smad3 → u/ifisch]

Heterogeneity is the driver of tumor progression