Decoding Decades-Old Samples: The Genomic Power of FFPE in Modern Drug Development

Formalin-fixed paraffin-embedded (FFPE) specimens have long been a cornerstone of histopathology, preserving tissues for diagnostic and research purposes. Now, these decades-old samples are emerging as powerful tools in modern drug development, especially in genomics-driven research. Stored in biobanks worldwide, FFPE specimens represent a vast repository of clinically annotated materials, providing a unique window into historical patient populations and disease conditions. From rare diseases to chronic illnesses, these archived samples are fueling discoveries that shape the future of medicine.

FFPE specimens encompass a wide variety of tissue types, including tumor biopsies, normal tissue controls, organ samples, and even samples from infectious disease outbreaks. These specimens capture a moment in a patient’s medical history, preserving the genomic landscape of diseases such as cancer, autoimmune disorders, and infectious diseases like tuberculosis or hepatitis. The breadth and diversity of these samples make them invaluable for retrospective genomic studies, enabling researchers to examine how diseases evolve over time and respond to therapies.

Cancer research has particularly benefited from the genomic analysis of FFPE samples. Tumor biopsies stored in this format have provided insights into genetic mutations, tumor heterogeneity, and mechanisms of resistance to therapy. For instance, archived lung cancer specimens have been used to identify key mutations in the EGFR gene, leading to the development of targeted therapies. Similarly, FFPE samples from breast cancer patients have aided in understanding the genomic differences between subtypes, guiding precision oncology approaches.

In the realm of infectious diseases, FFPE specimens have proven instrumental in studying pathogens and host-pathogen interactions. Biobanked tissues from historical outbreaks allow researchers to explore the genomic evolution of viruses and bacteria, identify potential drug targets, and understand immune responses. Decades-old FFPE samples from tuberculosis patients, for example, have been used to study the genetic basis of drug resistance, informing the development of new treatments.

Chronic inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease, also benefit from the retrospective study of FFPE specimens. Tissue samples from patients with well-documented clinical histories enable researchers to investigate the genomic drivers of inflammation and disease progression. These insights pave the way for biomarker discovery and the development of targeted therapies that modulate immune responses.

Despite the age of these samples, advances in molecular techniques have unlocked their potential. Technologies like next-generation sequencing (NGS), quantitative PCR, and microarray analysis have enabled high-quality genomic data extraction from FFPE specimens. Researchers can now sequence DNA and RNA, even from tissues stored for over 50 years, with remarkable accuracy. This has been a game-changer for retrospective studies, allowing for the integration of historical clinical data with modern genomic insights.

The challenges associated with FFPE samples, such as nucleic acid degradation and variability in fixation protocols, have been addressed through optimized extraction and quality control methods. These improvements ensure that even decades-old specimens can yield reliable genomic information, enhancing their utility in drug discovery and biomarker validation.

Beyond their scientific value, FFPE specimens offer a practical advantage: they are often the only source of tissue available for rare diseases and historical cohorts. In diseases like sarcomas or rare genetic disorders, where patient numbers are limited, FFPE samples provide an irreplaceable resource for understanding disease mechanisms and identifying therapeutic opportunities.

As genomics continues to drive drug development, the relevance of FFPE specimens will only grow. Their ability to connect the genomic landscapes of the past with the therapeutic innovations of the future makes them a cornerstone of modern biopharma research. By decoding decades-old samples, researchers are not just studying history—they are building the foundation for tomorrow’s medical breakthroughs.

Recent Published Studies Utilizing FFPE Specimens:

100,000 Genomes Project Pilot Study: This study performed whole-genome sequencing on patient-matched fresh-frozen (FF), FFPE, and germline biospecimens from 184 cancer patients. It demonstrated that, despite challenges, FFPE samples could be effectively used for genomic analyses, paving the way for their inclusion in large-scale genomic projects.1

Single-Cell Analysis of FFPE Tissues in Lung Cancer: Researchers conducted single-cell RNA sequencing on FFPE samples from non-small cell lung cancer patients. This approach enabled the study of retrospective samples, allowing for the examination of cell-type quantities and gene expression patterns, which are crucial for understanding tumor microenvironments and guiding therapeutic strategies.2

Whole-Exome Sequencing in Gastrointestinal Stromal Tumors (GIST): A pivotal study compared whole-exome analysis data from FFPE and FF samples of GIST patients. The high degree of concordance for all variants found, including novel somatic variants, highlighted the reliability of FFPE samples for high-throughput genomic studies, even in complex tumor types.3

These cases exemplify the successful application of FFPE specimens in genomic research, underscoring their value in advancing our understanding of various diseases and informing drug development.

Expanding the Genomic Frontier with FFPE Specimens and Specialized Capabilities

As genomics continues to transform drug development, FFPE specimens stand out as a vital resource bridging historical data with cutting-edge research. These samples not only connect the genomic landscapes of the past with the therapeutic innovations of the future but also offer a unique opportunity to deepen our understanding of disease progression, therapeutic responses, and biomarker development. Their relevance is particularly profound in fields where archived tissues provide the only means to study rare diseases, historical cohorts, and long-term clinical outcomes.

Avrok Biosciences provides essential expertise in maximizing the research potential of FFPE specimens for retrospective genomic studies. With advanced capabilities in biospecimen procurement, molecular extraction, and high-throughput analysis, Avrok ensures researchers can derive maximum value from decades-old samples. Their expertise in next-generation sequencing (NGS), quantitative PCR, and single-cell RNA sequencing is especially critical for overcoming the technical challenges associated with FFPE specimens, such as nucleic acid degradation and variability in preservation. By providing access to high-quality, clinically annotated FFPE samples and offering state-of-the-art genomic services, Avrok enables researchers to conduct robust retrospective studies that integrate molecular insights with historical clinical data. This seamless alignment of technology, expertise, and innovation exemplifies the transformative potential of FFPE specimens in modern drug discovery.

In a rapidly evolving biopharma landscape, the importance of leveraging archived resources cannot be overstated. By combining the vast potential of FFPE specimens with technological advancements and expert capabilities like those offered by Avrok, researchers are equipped to decode the mysteries of diseases, validate biomarkers, and accelerate the development of targeted therapies. These efforts not only honor the legacy of decades-old samples but also pave the way for groundbreaking medical breakthroughs that will shape the future of healthcare. In the realm of drug development, where every discovery has the potential to save lives, the ability to extract genomic insights from archival specimens is nothing short of revolutionary.

1. Mathieson, W., Thomas, G. Using FFPE Tissue in Genomic Analyses: Advantages, Disadvantages and the Role of Biospecimen Science. Curr Pathobiol Rep 7, 35–40 (2019). https://doi.org/10.1007/s40139-019-00194-6

2.    10x Genomics.  Feb 1, 2024 A pathologist’s perspective: Advantages of using FFPE tissues for single cell analysis.  10x Genomics Blog

www.10xgenomics.com/blog/a-pathologists-perspective-advantages-of-using-ffpe-tissues-for-single-cell-analysis

3   Astolfi, A., Urbini, M., Indio, V. et al. Whole exome sequencing (WES) on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in gastrointestinal stromal tumors (GIST). BMC Genomics 16, 892 (2015). https://doi.org/10.1186/s12864-015-1982-6