Cancer is (usually) caused by acquired genetic change. Whenever a cell divides it must copy the roughly 6 billion nucleotides that make up our DNA. Copying this DNA results in some mistakes and mistakes that occur in parts of the DNA controlling cell division or the death of cells results in uncontrolled cell division or failure of cells to die when they should.
Lymphocytes are always dividing, with new lymphocytes being formed to replace old ones that are no longer needed. As new ones are formed it is important that the old ones die, or else lymphocytes will accumulate.
Chronic lymphocytic leukemia (CLL) is caused by a variety of acquired genetic changes. Among the commonest are those that involve the BCL2 gene. (BCL stands for B cell leukemia.) The BCL2 gene product is a protein that interferes with cell death and the common change in this gene is over-expression. Lymphocytes that over-express the BCL2 gene do not die when they should.
Drugs that interfere with the product of the BCL2 offer the potential to control CLL. The New England Journal of Medicine (Roberts, A et al, January 28 2016, vol 374, No 4, p 311 report on a trial of venetoclax, an inhibitor of the BCL2 gene product. One hundred and sixteen patients with relapsed CLL were treated and 79% of these patients enjoyed a response. Side effects were tolerable and the commonest side effects were caused by the rapid death of leukemic cells.
The same journal reported on another new drug for treatment of CLL, acalabrutinib. This drug inhibits an enzyme called Bruton tyrosine kinase, an enzyme in the "B cell receptor signalling pathway" that leads to division of lymphocytes. Inhibition of this enzyme is a proven treatment for CLL. Acalabrutinib is a second generation bruton tyrosine kinase inhibitor that is expected to have fewer side effects than that first-in-class drug, ibrutinib. Sixty-one patients with relapsed CLL received acalabrutinib resulting in a 95% response rate.
Neither acalabrutinib nor venetoclax are FDA approved yet. Both drugs will need to undergo additional testing before submission for FDA approval. However current treatments for CLL are quite effective and new treatments are on the horizon.
These 2 drugs attack both of the problems that can cause cancer/leukemia: Failure of cells to die when they should (venetoclax) and excess cell division (acalabrutinib). Advances in the molecular biology of cancer and development of treatments aimed at the abnormal genes causing cancers are among the most exciting developments in cancer research. Most current cancer research is aimed at either this kind of drug or others that harness the power of the immune system.