Precision medicine in the era of multi-omics: can the data tsunami guide rational treatment decision?

Aldea, M.; Friboulet, L.; Apcher, S.; Jaulin, F.; Mosele, F.; Sourisseau, T.; Soria, J.-C.; Nikolaev, S.; André, F.

doi:10.1016/j.esmoop.2023.101642

Cited by 13 publications

(5 citation statements)

References 151 publications

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“…Current CGP in clinical care is restricted to DNA analysis for select genes and is not able to reveal multi-omics processes involved in cancers, such as methylation, cytokines, and protein expression. Several recent clinical trials have sought to enhance outcomes for cancer patients by combining DNA, RNA, and DNA methylation analyses [1,44,45]. In addition, the analysis of cytokines and immune cells is becoming crucial for predicting the efficacy of immunotherapy [2,46,47].…”

Section: Discussionmentioning

confidence: 99%

“…However, the recent progress of molecular techniques enabled multi-omics analysis to enhance our understanding cancer biology. In particular, next-generation sequencing (NGS) technology has revolutionized the simultaneous assessment of hundreds or even thousands of genes, not only in clinical research but also in clinical care [1,2]. Recently, it was reported that treatment with molecular targeted therapies based on comprehensive genomic profiling (CGP) significantly improved survival outcomes for patients with pancreatic cancer compared with patients who received non-molecularly matched therapies [3].…”

Section: Introductionmentioning

confidence: 99%

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Homologous Recombination Repair Gene Alterations Are Associated with Tumor Mutational Burden and Survival of Immunotherapy

Ito,

Kubo,

Kawaji

et al. 2023

Cancers

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Background: Comprehensive genomic profiling (CGP) has become generally accepted practice in cancer care since CGP has become reimbursed by national healthcare insurance in Japan in 2019. However, its usefulness for cancer patients is insufficient for several reasons. Methods: In an observational clinical study of FoundationOne® CDx, potential biomarkers were explored and the cause of testing failure was investigated. A total of 220 cancer patients were enrolled in the study during the period from 2018 to 2019 at Kyushu University Hospital. Results: The primary tumor sites of the 220 cases were breast (115), colon (29), stomach (19), and pancreas (20). The present dataset suggested that homologous recombination repair (HRR) gene alterations were positively associated with tumor mutational burden-high (TMB-high) (p = 0.0099). A public dataset confirmed that patients with HRR gene alterations had a higher TMB and showed significantly longer survival of immunotherapy. In the present study, 18 cases failed sequencing. A lower percentage of tumor cell nuclei was the most common reason for testing failures (p = 0.037). Cases that received neoadjuvant chemotherapy before sampling tended to fail testing. Conclusions: HRR gene alterations can be a potential biomarker predicting TMB-high and a good response to immunotherapy. For successful sequencing, samples with lower percentages of tumor cell nuclei and previous neoadjuvant chemotherapy should be avoided.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Homologous Recombination Repair Gene Alterations Are Associated with Tumor Mutational Burden and Survival of Immunotherapy

Ito,

Kubo,

Kawaji

et al. 2023

Cancers

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“…This approach involves analyzing the mitochondrial genome of a patient’s tumor to identify and tailor therapies that are best suited to the patient’s unique genetic profile. For instance, selecting small molecule inhibitors that specifically target identified mitochondrial mutations can be a direct outcome of this analysis ( 93 ). This method also has the potential to better predict a patient’s response to standard chemotherapy, thereby optimizing treatment regimens, reducing adverse effects, and improving overall treatment efficacy.…”

Section: Clinical Application and Therapeutic Prospectsmentioning

confidence: 99%

Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens

Chi,

Su,

Yan

et al. 2024

Front. Immunol.

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This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, and metabolomic studies, we dissected the mechanisms by which mitochondrial genetic variations dictate cancer progression. Emphasis has been placed on the roles of these genes in altering cellular metabolic processes, signal transduction pathways, and immune system interactions. We further explored how these findings could refine therapeutic interventions, with a particular focus on precision medicine applications. This analysis not only fills pivotal knowledge gaps about mitochondrial anomalies in pancreatic cancer but also paves the way for future investigations into personalized therapy options. This finding underscores the crucial nexus between mitochondrial genetics and oncological immunology, opening new avenues for targeted cancer treatment strategies.

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“…Future plans for this precision cancer medicine ecosystem include expanding the drugs included in FINPROVE while also allowing drug combinations especially for hematologic malignancies. Moreover, a deeper understanding on the molecular underpinnings of response and resistance of tumors to targeted treatments is urgently needed to enhance precision oncology approaches as it is unknown why some of the patients with the same molecular alteration respond and some fail to respond to the same therapy [6].…”

mentioning

confidence: 99%

A national precision cancer medicine implementation initiative for Finland

Jalkanen,

Alanne,

Iivanainen

et al. 2024

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To the Editor -The adaptation of nationwide genomic profiling and personalized cancer therapy in Finland has been challenging due to the lack of a uniform framework and funding. Meanwhile, increasing evidence demonstrates a clear benefit from precision medicine in cancer care [1,2] while the need for more efficient therapies in hard-to-treat cancers is evident. Equally a challenge for these cancers remains in the lack of randomized trials.Work to implement precision cancer medicine at a national level in Finland, began in 2021 led by Helsinki University Hospital (HUS) and FICAN South to meet three goals: (1) to implement genomic profiling and precision cancer medicine as standard of care, (2) establish equal access to molecular diagnostics and clinical trials in precision medicine, (3) to increase the number of precision cancer medicine trials and open a national DRUP (Drug Rediscovery Protocol)-like clinical trial.A multidisciplinary study team including oncologists, hematologists, gynecological oncologists, pathologists, cancer researchers, molecular and clinical geneticists was formed. This nationwide working group had the common aim to enable access to personalized cancer therapy for all patients in Finland irrespective of their residence. Early discussion amongst this initiative urged the need to equally engage stakeholders for reimbursement and sustained funding. Of equal importance was to explore the possibility of a public-private partnership for drug access and possibilities for shared pay for benefit funding. Political and financial support have revealed to be the most challenging steps within this initiative as consistent public funding is still lacking. Without international coordination with other major precision cancer medicine initiatives, especially the Dutch DRUP trial, the implementation would have been impossible.Tertiary care for cancer treatment in Finland is centralized to five university hospitals each governing a capture area of 0.7 to 1.7 M inhabitants. Each University hospital has a regional cancer center (FICAN South, West, East, North and Mid) that aims to promote equal access to diagnostics and treatment and, thus, the FICANs have played a major role in the precision cancer medicine initiative. During the past 3 years, we have therefore LETTER

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Precision medicine in the era of multi-omics: can the data tsunami guide rational treatment decision?

Cited by 13 publications

References 151 publications

Homologous Recombination Repair Gene Alterations Are Associated with Tumor Mutational Burden and Survival of Immunotherapy

Homologous Recombination Repair Gene Alterations Are Associated with Tumor Mutational Burden and Survival of Immunotherapy

Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens

A national precision cancer medicine implementation initiative for Finland

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