Why Chemotherapy works for some but not others

Posted by Jonathan on 4/26/2016 to Health
Why Chemotherapy works for some but not others

Why chemotherapy works for some but not for all. Alternative treatments.

I have worked in the chemistry of biological molecules (biochemistry) my whole life, but not in cancer research or cell biology. So after I got 2 cancers I am educating myself (and others) about cancer by reading original research papers.
1. Do we need to strengthen our immune system to fight cancer?
If we don't have constant infections then our immune system is strong. We don't need anything to strengthen it more.
2. Why does not our immune system kill cancer?
Because cancer is our own cells and the immune system knows not to kill them. Cancer cells have signals of "self" on the surface.
3. How chemotherapy drugs work?
They chemically attack DNA of the cells when they divide because DNA is exposed during cell division. After their attack the cell dies. As cancer cells divide very frequently, the chemo drugs kill mostly cancer cells and much less normal cells. There are also fast dividing normal cells like white blood cells or hair follicles. But they can recover after the treatment.
4. Can cancer return after chemotherapy and why?
Cancer is not a homogeneous mass. It's a combination of many subclones with different mutations that are unique for every person. It's like a tree with many branches. The growth of cancer tumor occurs via branched clonal expansion. Chemo drugs may kill >99% of the tumor, but a tiny % of cells might survive due to some specific mutations in their DNA. It's called a minimal residual disease. This clone of cells with these specific mutations that helped them to survive becomes drug resistant. The tumor from the drug resistant clone proliferates also by branched clonal expansion and becomes very heterogeneous, so no new drug can kill the whole tumor 100%. It's the biggest problem in cancer research.
5. Alternative treatments?
Cancer is so complicated that without understanding its mechanism and cell biology you cannot cure cancer by home made remedies. They might have a placebo-like effect and people feel that they are doing something for their cancer.
6. How do the new immunotherapies work?
They block the signals of "self" on cancer cells or signals on immune cells (checkpoints) that recognize those "self" signals. There are many checkpoints on immune cells and there are many signals of "self" on cancer cells. Examples: PD-L1, PD-L2, CD47 of "self" signals. Other immunotherapies teach our immune cells to recognize cancer despite "self" signals.