BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: oncogenes

Customizing Cancer?

Oncologists are moving toward a future in which cancer treatment is customizable and specific to each patient. This is achieved through genomic testing. Medical News Today: Pancreatic cancer splits into four types, says genome study

As genes differ from person to person, the information from genomic testing is unique to each. This speaks to what we’ve learned recently in bio class about how cellular mutations cause cancer. Changes to the DNA of a cell, specifically to genes that control the cell cycle, could result in oncogenes. But, I digress. The drawback of this type of treatment is that oncologists are met with so much information that it becomes not useful,  making the treatments less personal than they should be.

CHALLENGING GENETICS

The reason for this is due to the inability to identify which test will be most useful for each patient. When genetic data is obtained, what it means for the patient isn’t exactly clear. The example given in an article by Andrew Ip states that “several inhibitors of the enzyme anaplastic lymphoma kinase (ALK) have proven effective in treating lymphoma, non-small cell lung cancer, and neuroblastoma, while other findings suggest one of the inhibitors can treat pediatric oncology patients”. Although information was found from research specifically for ALK, it appears that much more is affected by these inhibitors making it less “personalized” than intended. 

Another reason as to why genomic testing is so difficult is accessibility. It can be difficult to get the treatments to patients due to health insurance limitations. In another instance, according to Andrew, “oncologists in community settings … had difficulty handling tumor samples, faced long turnaround times for laboratory tests, and had limited access to targeted therapies. To make it more difficult, next-generation sequencing results are often provided as a pdf, which cannot be digitally integrated with a patient’s electronic health records”. It appears altogether that oncologists are hindered by the lack of seamless integration of genomic testing into daily scenarios.

THERE IS HOPE

Although it appears that oncologists are overwhelmed, there is progress being made to support them. 

At the Hackensack Meridian Health John Theurer Cancer Center, where Andrew practices oncology, genomic testing was put into action. An ill patient had two separate biopsies done, and the findings of both contrasted each other greatly. One specified that the cancer identified was incurable, while the genomic sequencing depicted the cancer as curable. The patient was treated with chemotherapy and made quick improvement. 

The Genomic Testing Cooperative joined with Hackensack Meridian Health to implement an “in-house genomic profiling center”. As stated in Andrews article, the center “analyzes 434 genes for solid tumors, searching for DNA and RNA mutations and chromosomal structural abnormalities. For blood cancers, the service generates a 177 gene panel hematology profile”.

This isn’t all. A new database to which will aid oncologists in using the genomic results, cancer types, cancer medicines and patient outcomes is being built there as well.

FUTURE ADVANCES

In order to fully take advantage of genomic sequencing, companies are turning toward artificial intelligence. The goal is for AI to be able to use information from genomics, drug trials, patient demographics, and past scientific research to provide its own efficient course of action. This is called a clinical decision support system or CDS. IBM Watson was to be a CDS but did not suffice.

Until then oncologists take what Andrew describes as a “holistic approach to care”. This involves working with multidisciplinary teams made up of radiologists, pathologists, medical oncologists, radiation oncologists, and surgeons. Altogether they are known as molecular tumor boards. It’s fascinating to see just how much goes into making cancer care especially personalized to each patient.

The Role of Metabolism and Epigenetics in Cancer Development

Cancer most commonly is defined as a “perpetuating mass of dystregulated cells growing in an uncontrolled manner”, however the meaning can be further related to epigenetics, for they appear to be very much interconnected.  Another definition of cancer goes on to note this relationship as the “dynamic genetic and epigenetic alterations that contribute to cancer initiation and progress.” Recent research shows that if epigenetics is disrupted, it might switch to oncogenes or shut down tumor suppressors. Either way, this would lead to the development of tumor cells that would cause cancer. We are already aware of the fact that chemical modification affecting the packaging of our DNA can switch genes on and off. The first time that became aware of an epigenetic code, we learned that that code chemically labels active or inactive genetic information. The focus of epigenetics is on the change caused by the modification of gene expression, not the alteration of the code itself. With recent discoveries through research on epigenetics and its relation to cancer, we learned that there must be a balance of “writers” and “erasers” for the cells. Recent data has shown that methyltransferase EZH2 is an epigenetic writer that is hyperactivated in many cancers, specifically melanomas and lymphomas. This recent research also shows KDM3A (member of the jumonji histone lysine demthylase family) as an epigenetic eraser. KDM3A fulfills an oncogenic role by activating a network of tumor promoting genes. Epigonomic changes also allow tumor cells to evade the immune system so that these cells can thrive and divide without the disruption of the immune system. Ultimately, there are two potential pathways that epigenomic regulators can cause cancer. The first is the result of too much epigenetic activation, which can lead to oncogenes. The second is too much epigenetic protection that conversely blocks tumor suppressor genes. DNA hypermethylation causes the silencing of tumor suppressor genes.

Both of these methods would lead to the development of cancer. Epigenetic regulation involves methods including histone regulation, DNA methylation, and changes in noncoding RNAs such as miRNAs. One of the challenges of studying cancer and researching possible vulnverabilities in pathways is that they are often disrupted by epigenetics. The recent studies also have shown that there are close ties between epigenomic (analysis of global epigenetic changes across many genes) changes and metabolites, or human cellular chemistry. Metabolites initiate, target, or maintain epigenetic factors with the transcriptional complex, and cooperation with them metabolites can target, amplify or mute these coded responses. Since the fields of both epigenetics and metabolism are still developing a great deal, there is hope that these insights with regards to cancer and regulating gene expression to prevent the development of cancer will allow for more precision in targeting cancer, specifically when existing methods of therapy fail to work sufficiently.

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