Classifying breast cancer using IntClust to improve treatments

Breast cancer is heterogeneous in genetic composition. To improve treatments for this disease, Scientists have developed a classification system called IntClust that classifies it into 10 different subtypes.

Cancer arises from genetic changes in somatic cells. As known through research and observation, breast cancer is not one single disease -the mutations in the genes that cause varied cancers are not similar, and this is why tumors respond differently to treatment and grow at different rates. Currently, there are 2 key markers that clinicians use to predict response to treatments.

Spotting advances in tumor genetics and creating a system to diagnose tumor types is a primary objective of cancer scientists. For this purpose, researchers have developed the IntClust system, which uses genomic technology to more accurately pinpoint which type of breast cancer a patient has, and therefore what treatment would be most appropriate.

To validate this system, researchers examined the 997 tumor samples and 7,544 samples from public databases, along with the genomic and clinical data(such as data from the Cancer Genome Atlas). They respectively utilized IntClust system and two main systems in use today- PAM50 (five subtypes) and SCMGENE(four subtypes).

The research, published in the journal Genome Biology, shows that IntClust was at least as good at predicting patients' prognosis and response to treatment as the existing systems. With clinical significance, IntClust system identified a previously unnoticed subgroup of tumors in just 3.1% of women with very poor survival rates, which appeared to be resistant to treatment. Identifying the genomic signatures for this group could flag up these high risk cancers early, and having the genomic data for these could aid in the investigation of new avenues to treat this type of cancer.

Researchers from Harvard University announced last week they may have found an ALS therapy. When they blocked the gene for prostanoid receptor DP1 in ALS-model glial cells in a dish, they found neurons made from human embryonic stem (Es) cells were protected from death.

When they created ALS (amyotrophic lateral sclerosis) mice with that same gene deleted, the mice lived 6.7 percent longer. This finding helps validate the idea that neurons made from human stem cells. The 6.7 percent survival increase may rise even more, if/when their DP1 antagonist is given with a drug they earlier found has anti-ALS properties.

In Science Translational Medicine, the Eggan team reported creating motor neurons from green fluorescent protein (GFP)-expressing ES cells. These were then co-cultured with either normal cells, or SOD1 mutant glial cells, from neonatal mice. (SOD-1 is a gene mutated in a subset of ALS patients.) After ten days, they found the glial cells from the SOD1 mice caused a 55 percent decrease in motor neurons— compared to neurons co-cultured with normal glial cells.

the DP1 receptor is a critical mediator of glial toxicity to motor neurons in a stem cell model of ALS. Elimination of even a single allele of the gene encoding this receptor significantly extended the life span of the most widely studied ALS mouse model. Inhibition of the DP1 receptor is a rational strategy for slowing the negative impact of microgliosis in ALS.

Chronic treatment with a selective DP1 antagonist protected the neurons from toxic SOD1 glia, the team reported. The team then found an activator of DP1 caused a 49 percent decrease in motor neurons, similar to the effect of SOD1 mutant glia. The team also found the DP1 inhibitor acted on glial cells, which then impacted neurons. it is still unclear to what extent findings from stem cell models will be predictive of outcomes in vivo, this provides in vivo validation that DP1 suppression is a relevant therapeutic strategy in ALS.

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