Is Tracking Genomic Evolution the Future of Cancer Drug Discovery?

Is Tracking Genomic Evolution the Future of Cancer Drug Discovery?

Table of Contents

Challenges of Tumor Heterogeneity

It has long been known to researchers that tumors are like fingerprints: they may share common features, but no two are exactly alike between people. At a molecular level, researchers now understand that even within one tumor, there will be many distinct populations of cells, each harboring their own mutations and potentially responding differently to treatments.

Full characterization of a tumor can thus only be obtained through genomic profiling of multiple distinct regions of a given tumor. However, a long-term study began in 2014 to add yet another layer to tumor profiling – time. The TRACERx study (tracking cancer evolution through therapy) has published five recent papers in Nature highlighting their findings thus far in non-small cell lung carcinoma (NSCLC).

Breaking Down Tumor Evolution

Genomic analysis of 421 individuals and 1,644 tumor regions revealed specific patterns of genomic changes over the course of a tumor’s evolution. This included tendencies for mutations in MYC and receptor tyrosine kinases to produce effects that manifested early in a tumor’s evolution and thus were found in all of the subsequent populations of cells, while mutations in TP53 and KRAS were more often linked to later-stage mutations found in distinct subpopulations of cells.

Findings like these can help with drug target prioritization, identifying drug targets related to genes and mutations that are more likely to be found throughout the tumor rather than only targeting a subset of cells. Another paper found that platinum-based chemotherapies contributed to tumor evolution and heterogeneity, highlighting a consideration for designing drugs for use after a relapse from a chemotherapy regimen.

Effects on Immunotherapy 

Intratumor heterogeneity is not limited to cancer cells, either. Immune cell infiltration will vary in different regions of the tumor, affecting the ability of immunotherapy drugs to reach all of the cells. Both tumor and immune cell heterogeneity are being developed as biomarkers to predict patient response to different drugs.

Tools like biomarkers for patient stratification and companion diagnostics will be central to the cancer drug development pipeline as treatments become more tailored and specific to cancer cell subtypes. Comprehensive genomic profiling will be a critical tool for identifying new drug targets as well as for the effective diagnosis and administration of emerging precision therapies.

Outsourcing Bioinformatics Analysis: How Bridge Informatics Can Help

Groundbreaking studies like these are made possible by technologies like RNA-seq, and advances that have made whole genome sequencing, sample processing, and data analysis faster, cheaper, and more accessible than ever before. From pipeline development and software engineering to deploying existing bioinformatics tools, Bridge Informatics can help you on every step of your research journey.

As experts across data types from leading sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing, and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here to schedule a free introductory call with a member of our team.

Jane Cook, Biochemist & Content Writer, Bridge Informatics

Jane Cook, the leading Content Writer for Bridge Informatics, has written over 100 articles on the latest topics and trends for the bioinformatics community. Jane’s broad and deep interdisciplinary molecular biology experience spans developing biochemistry assays to genomics. Prior to joining Bridge, Jane held research assistant roles in biochemistry research labs across a variety of therapeutic areas.

While obtaining her B.A. in Biochemistry from Trinity College in Dublin, Ireland, Jane also studied journalism at New York University’s Arthur L. Carter Journalism Institute. As a native Texan, she embraces any challenge that comes her way. Jane hails from Dallas but returns to Ireland any and every chance she gets. If you’re interested in reaching out, please email [email protected] or [email protected].

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