What makes cancer cells different from ordinary cells in our bodies? Can these differences be used to strike at them and paralyze their activity? Cancer researchers have been debating this question since the mid-19th century.
A new study from shows, for the first time, how an abnormal number of chromosomes (aneuploidy) -- a unique characteristic of cancer cells that researchers have known about for decades -- could become a weak point for these cells. The study could lead to the development of future drugs that will use this vulnerability to eliminate the cancer cells. The study was published in the journal Nature.
Aneuploidy is a hallmark of cancer. Normal human cells contain two sets of 23 chromosomes each, one from the father and one from the mother. But aneuploid cells have a different number of chromosomes. When aneuploidy forms in cancer cells, the cells not only "tolerate" it, but it can even advance the progression of the disease. The relationship between aneuploidy and cancer was discovered over a century ago, long before it was known that cancer was a genetic disease and even before the discovery of DNA as hereditary material.
According to the senior author, aneuploidy is the most common genetic change in cancer. Approximately 90% of solid tumors, such as breast cancer and colon cancer, and 75% of blood cancers are aneuploid in nature. But researchers' understanding of the how aneuploidy contributes to the development and spread of cancer has been limited.
In the study, the researchers used advanced bioinformatics methods to quantify aneuploidy in approximately 1,000 cancer cell cultures. They then compared the genetic dependency and drug sensitivity of the cells with a high level of aneuploidy to those of the cells with a low level of aneuploidy.
They found that aneuploid cancer cells demonstrate heightened sensitivity to damage to the mitotic checkpoint - a cellular checkpoint that ensures the proper separation of chromosomes during cell division. They also discovered the molecular basis for the heightened sensitivity of aneuploid cancer cells.
The authors unidentified a specific mitotic kinesin, KIF18A, whose activity was perturbed in aneuploid cancer cells. Aneuploid cancer cells were particularly vulnerable to depletion of KIF18A, and KIF18A overexpression restored their response to spindle assembly checkpoint inhibition.
The study has important implications for the drug discovery process in personalized cancer medicine. Drugs that delay the separation of chromosomes are undergoing clinical trials, but it is not known which patients will respond to them and which will not. The results of this study suggest that it will be possible to use aneuploidy as a biological marker to identify patients who will respond better to these drugs.
"It should be emphasized that the study was done on cells in a culture and not on cancer patients. In order to translate it to treatment of cancer patients, many more follow-up studies must be performed. Still, even at this stage it is clear that the study could have a number of medical implications," the senior author says.
https://www.aftau.org/news_item/new-tau-study-reveals-achilles-heel-of-cancer-cells/
https://www.nature.com/articles/s41586-020-03114-6
Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition
- 1,079 views
- Added
Edited
Latest News
How brains convert sounds t…
By newseditor
Posted 12 May
Mice with traits of Tourett…
By newseditor
Posted 11 May
Intermittent fasting protec…
By newseditor
Posted 11 May
Microfluidic systems resemb…
By newseditor
Posted 11 May
Neurotransmitter classifica…
By newseditor
Posted 11 May
Other Top Stories
A new mechanism that accelerates aging of adipose tissues
Read more
The mechanism underlying orofacial movements during reward processi…
Read more
Newly identified lipid in breast milk might reduce cerebral palsy i…
Read more
Appetite controlling gut hormone doubles as an immune regulator
Read more
How immunity contributes to ageing and neurodegeneration
Read more
Protocols
Improved detection of DNA r…
By newseditor
Posted 09 May
Single-cell adhesive profil…
By newseditor
Posted 07 May
Parasympathetic neurons der…
By newseditor
Posted 07 May
Non-invasive measurements o…
By newseditor
Posted 05 May
A validation strategy to as…
By newseditor
Posted 04 May
Publications
Differential representation…
By newseditor
Posted 12 May
Glucose hypometabolism prom…
By newseditor
Posted 12 May
Organellophagy regulates ce…
By newseditor
Posted 12 May
Decoding mitochondria's rol…
By newseditor
Posted 11 May
APOE2 gene therapy reduces…
By newseditor
Posted 11 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar