One reason cancer drugs do not work equally well in everyone: chromosomal abnormalities!

Immunotherapies offer an effective treatment opportunity by preventing cancer cells from becoming “invisible” to the immune system. However, some patients respond very well, while success is much lower in others. Researchers have been investigating why patients respond differently to immunotherapies. Science published a study in January 2017 finding that chromosomal abnormalities in cancer cells could be an important marker for determining which patients will benefit from immunotherapy.

The fundamental cause of cancer is the accumulation of damage in our DNA. As a result of this damage, the genes controlling cell proliferation and relationships between cells work in ways that support cancer formation. Our genes are located in structures called chromosomes. A healthy person has 46 chromosomes, arranged in pairs: 23 inherited from the mother and 23 from the father. Different or reduced chromosome numbers cause developmental disorders and deaths.

Cancer cells have different chromosome numbers!

One of the 10 hallmarks of cancer is abnormalities in genetic structure and chromosomes. Most cancer cells have been found to have missing or extra chromosomes. For example, while a human cell has 46 chromosomes, a cancer cell may have 45 or 47. Missing or extra chromosomes in cancer cells are called aneuploidy . Recently, the idea that aneuploidy in cancer cells may be an important marker for monitoring the course of cancer treatment has gained attention. In this study, tumor samples from 12 cancer types, 5000 in total, were examined to observe the effects of differences in chromosome number.

According to the research results,

• Tumors with many chromosomal abnormalities were found to keep inactive the genes that enable their recognition by the immune system.
• Patients whose tumors have many chromosomal abnormalities have a very poor disease course (progression).
• One of the study’s most important results was that patients with melanoma tumors containing many chromosomal abnormalities, in particular, benefited less from immune checkpoint inhibitors.

What does this study mean clinically?

• The idea that chromosomal abnormalities may be an important marker has begun to gain prominence.
• Chromosomal abnormalities were found to increase cancer cells’ “invisibility” to the immune system.
• Examining chromosomal abnormalities in a patient’s tumor sample may determine whether they will respond to immunotherapy.