Cookies

Like most websites The Pathologist uses cookies. In order to deliver a personalized, responsive service and to improve the site, we remember and store information about how you use it. Learn more.
Subscribe to Newsletter
Subspecialties Oncology, Omics, Genetics and epigenetics, Technology and innovation

Unraveling the Complexity of Intratumor Heterogeneity

Intratumor heterogeneity (ITH) is strongly associated with cancer progression, making it a hot area of research. In some cases, ITH is being used as a diagnostic marker – and certain HER2+ cancers already benefit from ITH assessments in pathology reports, which allow practitioners to predict effectiveness of targeted therapies. Although ITH exploration has been somewhat held back by the cost of clinical samples and specialist equipment, the field is moving forward – and a recent review in Nature Cell Biology (1) considers the progress made so far, hoping to “illuminate future directions.” One experimental model being used to investigate ITH combines molecular barcoding and multi-omic profiling at single-cell resolution, and the authors note that its utility has been demonstrated through the development of ClonMapper (2) – software that maps single-cell transcriptomics to clonality, thus allowing specific clones of interest to be studied. Another research avenue relies on CRISPR-based technologies; for example, by combining single-cell RNA sequencing and Cas9-enabled indels, researchers are able to reconstruct evolutionary descent and molecular drivers of metastasis.

The tumor microenvironment and cell-to-cell interactions are also fertile ground for investigation. Here, a number of different approaches are in play, say the authors, including in vitro and in vivo reporter systems, a hypoxia fate-mapping system, and the creation of an in vivo pH ratiometric bioluminescent sensor. All of these technologies can be incorporated into experimental models to gain greater insight into the factors that shape ITH.

Elsewhere, researchers have created a novel computational method – nicknamed HUNTRESS – that is capable of deducing mutational ITH from single-cell sequencing data. When tested on simulations and real-life tumor data, HUNTRESS is able to calculate a tumor’s progression with high probability – at a faster rate and with more accuracy than other methods. When it comes to the real life data, HUNTRESS’ inferred tumor progressions were consistent with “the best known evolution scenarios for the associated tumors.”

Based on recent research, artificial intelligence (AI) looks set to tackle a number of challenges currently plaguing ITH’s full transition into the laboratory – helping pathologists deal with rivers of data and a significant need for “number crunching.” But AI is only as powerful as the data with which it is fed, highlighting the importance of increasingly accurate experimental models.

Receive content, products, events as well as relevant industry updates from The Pathologist and its sponsors.
Stay up to date with our other newsletters and sponsors information, tailored specifically to the fields you are interested in

When you click “Subscribe” we will email you a link, which you must click to verify the email address above and activate your subscription. If you do not receive this email, please contact us at [email protected].
If you wish to unsubscribe, you can update your preferences at any point.

  1. Z Li et al., “Untangling the web of intratumor heterogeneity,” Nat Cell Biol, 24, 1192 (2022). PMID: 35941364.
  2. C Gutierrez et al., “Multifunctional barcoding with ClonMapper enables high-resolution study of clonal dynamics during tumor evolution and treatment,” Nat Cancer, 2, 758 (2021). PMID: 34939038.
  3. C Kızılkale et al., “Fast intratumor heterogeneity inference from single-cell sequencing data,” Nat Comput Sci, 2, 577 (2022).
About the Author
George Francis Lee

Associate Editor, The Pathologist

Like most people, I didn’t know exactly what I wanted to do after university. But one thing was certain – writing would play a central role. Not one to walk the path most traveled, I decided to spend my next few years freelancing to hone my skills as a writer and further cement my love for language. Reaching people through writing is important to me and I look forward to connecting with thousands of people through Texere’s passionate audience.

Register to The Pathologist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:
  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Pathologist magazine

Register