Leonid Shunyakov, MD, hematologist/oncologist, Central Care Cancer Center, discusses how genomics have impacted personalized therapy in oncology.

In addition to using tumor mutational burden, gaining knowledge at the molecular level about how genes work and using that knowledge to guide therapy is another novel way of using next-generation sequencing (NGS), says Shunyakov. In kidney cancer, one of the most commonly mutated genes is 

. It is associated with activation of a certain inflammatory pathway, and whenever it is activated, there is a higher likelihood of response to immunotherapy.

However, NGS is not the answer to everything, explains Shunyakov. In addition to NGS, physicians have proteomics. Exosomes are produced by cancer and expulse microRNA. Shunyakov adds that the tumor has a 3D structure which is why there is tumor heterogeneity. Solid biopsies may not reflect everything. To get a more complete picture, physicians may use the combination of liquid and tissue biopsies.

There is also a very important role for the microbiome, states Shunyakov. At the 2018 ASCO Annual Meeting, physicians learned that akkermansia bacteria are associated with marked improvement in response to immunotherapy, and certain bacteria such as bacteroidetes are associated with “cold” immune signatures and lower responses to immunotherapy.

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Dr. Shunyakov on the Impact of Genomics on Personalized Therapy in Oncology

Leonid Shunyakov, MD, hematologist/oncologist, Central Care Cancer Center, discusses the impact of next-generation sequencing (NGS) in oncology.

Genomics is a huge part of oncology, says Shunyakov, but there are limitations to the technology. There is disparity between different assays, says Shunyakov. FoundationOne and Guardant360 are the 2 most commonly used assays in practice, but the discordance rate is about 70% and the concordance rate is about 20% to 25%.

Physicians have used NGS to guide treatment selection in patients with a single driver mutation, but most cancers are much more complex and have more than one driver, explains Shunyakov.

Most recently, the CheckMate-227 trial assessed tumor mutational burden (TMB). The study was published in the 

 and showed that high TMB could potentially be used as a predictive response to the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) in non—small cell lung cancer. The study showed a 1-year 43% progression-free survival rate in the combination group compared with 13% in chemotherapy.

Assessing TMB is just one of many novel ways of using NGS, says Shunyakov. Gaining knowledge at the molecular level about how genes work and using that knowledge to guide therapy is another novel way of using NGS.

Leonid Shunyakov, MD

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Dr. Shunyakov on the Impact of Genomics on Personalized Therapy in Oncology

Dr. Shunyakov on the Impact of Next-Generation Sequencing in Oncology