Advancing Cancer Research with Modern Sequencing Tools

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Benjamin Atha has over 9 years of experience working in molecular biology laboratories. He received his B.A. in biology from Hood College, and also received his M.S. in biological sciences from Towson University where his thesis focused on protein functions and post-translation modifications. After graduation, Ben began working with next-generation sequencing at Walter Reed Army Institute of Research and for the USDA. He now writes for Biocompare and serves as the editor for SEQanswers.

June 18, 2025

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Cancer continues to be the leading cause of death worldwide, and its widespread impact means that most people have either faced it themselves or supported someone who has.¹ Although our understanding of the many diseases classified as cancer has advanced, there are still many unknowns. One of the most powerful tools driving cancer research forward is next-generation sequencing (NGS). New platforms, techniques, and analysis methods are enabling researchers to uncover critical insights into cancer biology.

NGS applications in cancer biology

NGS plays an important role in cancer research by offering a variety of methods to investigate the molecular mechanisms underlying tumor development and progression. Cancer arises from dysregulated cellular processes, and researchers are increasingly turning to sequencing approaches that integrate genetic, epigenetic, and transcriptomic data to understand them, stated Ellie Juarez, Ph.D., Global Market Segment Manager, Oncology, at Oxford Nanopore Technologies. This multiomic approach provides a more complete view of tumor biology and supports the discovery of biomarkers for diagnosis and therapeutic intervention.

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Rob Tarbox, Vice President of Product and Marketing at Complete Genomics, noted that comprehensive molecular profiling is one of NGS’s most powerful contributions to cancer research. Key applications include identifying actionable mutations for targeted therapy and tracking minimal residual disease through circulating tumor DNA (ctDNA). Tarbox added that researchers are also using NGS to study tumor heterogeneity and the tumor microenvironment, particularly through single-cell and spatial transcriptomics, which support more precise diagnoses and personalized treatments.

Tyler Lopez, Ph.D., Associate Director of Biochemistry at Element Biosciences, shared that NGS is expanding how researchers study tumor behavior by combining molecular and phenotypic data. He also emphasized the value of integrating RNA expression, protein levels, and cellular morphology to better understand pathway activity and treatment response. While whole-genome and targeted sequencing remain important for identifying actionable mutations, Lopez noted that integrated single-cell and spatial data reveal functional patterns not captured by traditional sequencing methods.

Modern sequencing technologies

The last decade has seen a rise in sequencing innovation, with new technologies bringing improved resolution and flexibility. These platforms vary in technical parameters, including read length, accuracy, throughput, and chemistry. Each of these differences directly impacts their use in cancer research.

“Detecting rare variants or low-frequency mutations—especially in heterogeneous tumors or liquid biopsies—requires high output, excellent accuracy, and affordability,” stated Tarbox. He noted that cancer research often resembles finding a needle in a haystack, and that technical parameters greatly influence how researchers design their studies. According to Tarbox, short-read, high-throughput sequencing remains the most practical option for many cancer studies because these experiments often rely on sampling large amounts of data at low cost and high quality. “Our T1+ platform was developed with these needs in mind. It delivers higher output, improved fidelity, and significantly reduced cost per gigabase, in an accessible instrument format, helping more researchers scale their efforts without compromise,” Tarbox added.

Long-read platforms, on the other hand, offer distinct advantages for resolving complex genomic alterations. Juarez noted that while short reads have driven much of the progress in cancer genomics, they have limitations with structural variants, gene fusions, and deep-intronic mutations. However, platforms capable of sequencing long fragments are closing this gap. “Differences in platform design, particularly the ability to deliver rapid, real-time sequencing results, as exemplified by Oxford Nanopore, are reshaping the potential for near-instant clinical decision-making,” Juarez emphasized. These capabilities include generating long reads, directly detecting epigenetic modifications, and sequencing native DNA and RNA in real time.

In agreement with this broader view, Lopez noted that every sequencing approach offers strengths and trade-offs. Short reads are ideal for high-throughput studies focused on variants and gene expression, whereas long reads provide better resolution of structural variation and haplotype phasing. With growing interest in functional insights from diverse cell populations, Lopez shared that researchers are turning more often to multiomic and spatial technologies. “Platforms like our AVITI24 offer a distinct advantage by combining single-cell resolution with multiomic readouts, helping researchers link genetic perturbations to protein activity and cellular morphology within the same experimental run,” stated Lopez.

Advances and real-world impact

Recent developments in sequencing are beginning to deliver tangible benefits in real-world cancer research and clinical practice. “One of the most promising recent advances in cancer research is the growing ability to interrogate DNA methylation patterns at high resolution and across the whole genome,” said Juarez.

Methylation profiling has been especially impactful in central nervous system (CNS) tumors, where it improves diagnostic accuracy by distinguishing subtypes with different prognoses. Juarez shared that researchers are now exploring the use of Oxford Nanopore’s real-time methylation analysis during CNS tumor surgeries, a process that has traditionally relied on microarrays.²In addition, Juarez noted that Oxford Nanopore’s ability to produce long sequencing reads improves coverage and mapping in noncoding regions, advancing the study of deep intronic variants. As highlighted in a study by Tom Walsh and Mary-Claire King, these underexplored variants may disrupt key cancer pathways, even in well-studied genes.³

“Single-cell multiomic methods and spatial transcriptomics are reshaping how we study cancer progression and therapeutic resistance,” stated Lopez. These methods provide detailed insight into individual cell behavior. Lopez explained that with technologies like AVITI24, researchers can map pathway activity in its native context and explore how gene expression and protein dynamics interact to drive tumor behavior. This integrated approach has helped reveal conserved apoptotic signaling across cancer types, and identified pathway adaptations linked to tyrosine kinase inhibitor resistance in non-small cell lung cancer.^4,5 These findings demonstrate how same-cell multiomic profiling can streamline workflows, reduce variability, and uncover drug response mechanisms that traditional assays often miss.

Building on this progress, high-resolution spatial mapping techniques and ultra-sensitive liquid biopsies represent two of the most impactful areas of innovation in cancer biology. “These tools allow researchers to visualize gene expression in the tumor microenvironment or detect minimal residual disease with unprecedented sensitivity,” said Tarbox. A notable example is MD Anderson’s use of spatial transcriptomics to create 3D maps of the tumor microenvironment in gynecologic cancers.⁶ This approach revealed immune evasion mechanisms, along with potential biomarkers and therapeutic targets at single-cell resolution. Tarbox highlighted the STOmics platform as a key part of this progress and noted ongoing efforts to improve throughput, accuracy, and affordability to support broader use in clinical research.