Today I am going to embark on a new series of posts where I create for you brief, journalistic style breakdowns of high impact scientific publications. I am calling this series "Research News" (if anyone would like to create me a unique thumbnail for this series, please reach out to me on the steemSTEM Discord, and I can describe to you what I envision)

A consortium of researchers from prestigious institutions such as Memorial Sloan Kettering Cancer Center (in New York City), and the Dana-Farmer Cancer Institute (in Boston MA) have just published a work in Nature. Where they discuss the use of a SUMMET (a clinical trial composed of patients with a wide variety of histories and mutations) on some commonly identified mutations in two kinases (HER2 and HER3) which are found in a variety of cancer types.

Kinases are enzymes which have a specialized function in our cells. They attach phosphate molecules to various amino acids on other proteins. This is done for a variety of reasons including: activating (speeding up), deactivating (slowing down), and complex assembly (allowing several proteins to come together and make a larger protein machine). Thus the function of kinases are essential to the fine tuned, and interwoven web of enzyme activities that keep our cells running smoothly. If kinases go haywire, so do our cells, resulting in one of the many ways that we can develop cancer.

To date, little is known what the consequences of many of these identified mutations in the HER kinases are (and as a result, little is known about how to effectively treat them), some are thought to activate these enzymes (speeding them up) however most have not been characterized. What is known however, is that the mutations promote the development of cancer.

To tackle the generation of a broad swath of information regarding the viability of targeting the various mutant forms of the HER kinases, researchers embarked on a clinical trial where a large group of patients were treated with a drug that stops the functioning of these enzymes, called neratinib. It was noted which tumors responded positively or negatively to the treatment, and samples from those patients tumors were collected allowing for sequencing of each of the genomes. The information gained will allow for better understanding of the precise role that the mutated forms of these kinases play in the development of the patients cancers.

It also furthers our ability to perform modern 'Precision Medicine' where knowing the effect of a treatment down to the genetic level can enable doctors to pick and choose which drug should be used to combat which cancer causing mutation a future patient has. What this means is that the information contained in this study can be used to enable personalized therapies for each cancer sufferer possessing a HER mutation. It also illustrates the growing importance of geno-typing each patients cancer, and the power of modern DNA sequencing technologies.

The authors were able to extract information on 31 unique HER2 mutations and 11 unique HER3 mutations. These enzyme alterations were found in 21 different varieties of cancer including breast, lung and colon. Through their studies their observation of activity of the HER inhibitor (neratinib) down to the genomic level in a variety of the cancer types which was promising, though the authors reported that the response rates were still lower then currently approved therapies.

Still, the information presented in this study is of high impact as it suggests that targeting these mutations specifically could be effective especially in combination with other chemotherapy techniques. It also opens the door to the study of combination therapies where neratinib is used at the same time as another HER kinase inhibiting compound to determine whether more potent anti-cancer effects are observed on the various mutations identified as positive hits here.

Furthermore, the authors identified functional information on a variety of mutations to the HER kinases which were previously not understood. They found that many mutations which responded well to the treatment (they were using an inhibitor here, so mutants that were responders were those where the enzyme was sped up). This is important information as knowing what changes to enzyme activity result from which mutations will ALSO lead to much more effective treatments in the future as well.

The biology of cancer is exceedingly complex, information like that contained in this study is extremely important to help in the process of assembling a clearer picture of how our cells go awry. There is no easy answer for how best to treat cancer, however through intensive study and genotyping we are beginning to see the puzzle pieces slowly come together.

Sources

Text Sources

https://www.nature.com/articles/nature25475

Image Sources

Thumbnail Image, The Extracellular Domain of HER2

neratinib structure

SteemSTEM

If you haven't heard about the SteemSTEM project yet and are reading this post then I highly recommend you take a look into it! The SteemSTEM team has been working for over one year now to promote promote well written/informative Science Technology Engineering and Mathematics postings on Steemit. The project (@steemstem) seeks to build a community of science and technology lovers on steemit and ade in nurturing the growth of blogs that will make steemit a go-to source for science/tech information, news, and just generally fascinating content.

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