What Are Oncodomain Hotspots? How Does This Impact Cancer Drug Development?

What Are Oncodomain Hotspots? How Does This Impact Cancer Drug Development?

Researcher identifies oncodomain hotspots for cancer research

Scientists at the University of Maryland recently identified thousands of genetic mutations they believe contribute to cancer growth. By employing a unique statistical-analysis method they developed, the researchers identified genetic abnormalities shared within families of related proteins. These are mutations that could trigger cancer and it’s a discovery that could help us revolutionize drug development in this space.

The research was published in the PLOS Computational Biology journal and focuses on mutations in protein domains, or specific subsets of proteins. Even when encoded by different genes, various proteins can share these domains. Their unorthodox approach has since identified hundreds of these protein families which they have dubbed “oncodomains.”

Genomics Influence on Cancer Research

As you may already know, cancer is a disease of the genome. This is why progress in genomics has had such a significant impact on therapeutic development in this space. In the past, cancer drugs were more akin to cellular poisons; now the vast majority of new treatments are targeted at particular gene products. The more genetic products we discover, the greater the potential for new drugs. In fact, there are currently 800 different anticancer drugs in development.

Most tumors possess a group of structural genomic alterations. Cancer biologists have spent several decades trying to unravel these alterations’ meaning and importance; however, it’s the global genome characterization efforts that have taken tumor biology and the accompanying paradigm for cancer treatment to a whole new level. Genomics has been the catalyst behind cancer treatments’ unprecedented pace of advancement.

Disruptive technologies have enabled DNA sequencing to advance at rates we’d have never dreamed possible in the past. Not to mention that parallel progress across other fields has helped bring about numerous new sequencing methods. Some of these fields include:

  • Computation
  • Data storage
  • Miscroscopy
  • Nucleotide biochemistry
  • Polymerase engineering
  • Surface chemistry

While cancer genome biology, technology, and targeted therapeutics have progressed significantly, it’s only a start. An issue we’re still facing is that some new cancer drugs can make tumors disappear effectively, only to have the cancer come back full force a year later. This is because some of the cells developed mutations that make them resistant. Genome scientists are now working hard to find and target these potential mutations as well.

Why Personalized Cancer Treatments are Critical

The term “carcinoma” was first used by Hippocrates around 400 BC, and the earliest signs of cancer actually date back to fossilized bone tumors of ancient Egyptian mummies. This devastating disease has plagued us for centuries; however, we still don’t have a cure.

One of the main reasons we have still not been able to cure cancer is that it is an extremely heterogeneous disease. Not only do cancer cells differ from patient to patient, they even differ within a single patient. Because of the disease’s specific nature, precise and personalized treatments are needed.

Cancer is a huge focus of the precision medicine initiative. Precision medicine, also known as targeted therapy, stops (or attempts to stop) cancer from growing and spreading by targeting specific genes or proteins. Precision oncology works by trying to match the most effective treatment to an individual cancer patient based on that person’s genetic profile and the cancer’s genetic profile. At present, targeted therapy is often used in conjunction with chemotherapy and other treatments.

Not only does every single cancer patient possess a different genetic profile, but this profile can also change over time. Because cancer is not “one size fits all,” we should avoid this mentality when treating it. More patients will benefit if their therapeutic options are tailored to them, which is why personalized cancer treatments are necessary.

How Does ‘Hotspots’ Discovery Alter Future Research Efforts?

Scientists say that studying oncodomains, the “hotspots” for mutated proteins, could help identify new oncology drug targets.

Using a statistical rather than a gene-centric approach, Kann and her team identified these oncodomains, based on the number of somatic variants in one or more genes that contain the same domain. Oncodomain hotspots are positions in the oncodomain sites where somatic variants linked to cancer occur more frequently than would be predicted by chance. Some hotspot patterns were the same in various cancer types, while others were specific to a certain cancer.

Since protein domains are shared across different proteins, the researchers anticipate comparing genes within the same domain family could help assess whether or not rare variants could be functionally relevant.

“Because the domains are the same across so many proteins, it is possible that a single treatment could tackle cancers caused by a broad spectrum of mutated proteins,” senior study author Maricel Kann said in the release.

Conclusion

The medical community harbors high hopes for this novel discovery. Combined with the recent launch of the NCI Formulary and a greater focus on the patient, we’re predicting that cancer treatments will become significantly more effective over the next decade.

Though cancer is by no means a “one size fits all” disease, we could be much closer to Kann’s vision of a single treatment tackling a range of cancers. Because of our newfound knowledge of oncodomain hotspots and greater insight into the nature of mutated protein domains, we could be one step closer to a cure.

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