WGS/WES-RNAseq compared to targeted NGS in oncology: is there something to unlock?

Precision medicine stands as the holy grail of oncology, striving to elucidate the mechanisms of cancer origin and resistance, thereby fostering personalized patient care with maximum benefit and minimal toxicity. Although it is a beacon of hope, precision medicine studies exploring the usefulness of treatment tailoring have produced somewhat disappointing results over time due to various historical reasons: •The employed technique or panel often lacked comprehensiveness or suitability. For instance, when RNA sequencing is incorporated in addition to DNA sequencing, target identification with subsequent treatment tailoring can be increased by 10% or more. 1 Rodon J. Soria J.C. Berger R. et al. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat Med. 2019; 25: 751-758 Crossref PubMed Scopus (305) Google Scholar •Treatment tailoring was often dependent on drug availability and expert opinion rather than international evidence recommendations based on actionability evidence. 1 Rodon J. Soria J.C. Berger R. et al. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat Med. 2019; 25: 751-758 Crossref PubMed Scopus (305) Google Scholar , 2 Massard C. Michiels S. Ferte C. et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 2017; 7: 586-595 Crossref PubMed Scopus (488) Google Scholar , 3 Le Tourneau C. Delord J.P. Goncalves A. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015; 16: 1324-1334 Abstract Full Text Full Text PDF PubMed Scopus (777) Google Scholar , 4 Sicklick J.K. Kato S. Okamura R. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med. 2019; 25: 744-750 Crossref PubMed Scopus (381) Google Scholar •Frequently, drug availability posed challenges or the proposed drug–target pairs did not constitute selective inhibitors. 2 Massard C. Michiels S. Ferte C. et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 2017; 7: 586-595 Crossref PubMed Scopus (488) Google Scholar •Studies often included heavily pre-treated patients who were more likely to have resistant tumors. 2 Massard C. Michiels S. Ferte C. et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 2017; 7: 586-595 Crossref PubMed Scopus (488) Google Scholar , 3 Le Tourneau C. Delord J.P. Goncalves A. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 2015; 16: 1324-1334 Abstract Full Text Full Text PDF PubMed Scopus (777) Google Scholar , 4 Sicklick J.K. Kato S. Okamura R. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat Med. 2019; 25: 744-750 Crossref PubMed Scopus (381) Google Scholar