Ocean with island above the surface and octopus submerged below, suggesting that there’s more to some cancers than meets the eye

Tumori con fusioni TRK

Qual è il driver tumorale

Le alterazioni “actionable” possono essere presenti in diversi istotipi tumorali1,2

Dal 30% al 49%
È possibile riscontrare un’alterazione actionable in una percentuale che varia dal 30% al 49% dei pazienti sottoposti a profilazione genomica del tumore1,2

Le proteine di fusione TRK* sono spesso un driver oncogenico primario
in diversi tipi di tumore3,4

NTRK gene fusions are oncogenic drivers caused by genomic rearrangement
NTRK gene fusions are oncogenic drivers caused by genomic rearrangement
NTRK gene fusions are oncogenic drivers caused by genomic rearrangement
Immagini al solo scopo illustrativo
  • Nel tumore con fusione TRK, il gene NTRK ** si fonde con un gene non correlato, causando una sovraespressione della proteina TRK3,5-7
  • La ricerca ha identificato fusioni del gene NTRK  in oltre 20 tipi di tumori solidi comuni e rari3-5,7
  • Le proteine di fusione TRK possono escludere la presenza di altri driver oncogenici noti8

Test specifici sono in grado di individuare
i tumori con fusione TRK

Next-generation SequencingSequenziamento di nuova generazione (NGS)3,6,9,10
ImmunohistochemistryTest immunoistochimici pan-TRK (IHC)11
DNA fluorescence in situ hybridizationIbridazione fluorescente in situ del DNA (FISH)9,10,12
Reverse transcription polymerase chain reactionReazione a catena della polimerasi con trascrittasi inversa (RT-PCR)9,13
INSERIRE LA FUSIONE DEL GENE NTRK  NEL PROTOCOLLO DI ANALISI

*TRK: chinasi del recettore della tropomiosina.
**NTRK: recettore della tirosin chinasi neurotrofica.

Riferimenti: 1. 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(6):586-595. 2. Boland GM, Piha-Paul SA, Subbiah V, et al. Clinical next generation sequencing to identify actionable aberrations in a phase I program. Oncotarget. 2015;6(24):20099-20110. 3. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34. 4. Okimoto RA, Bivona TG. Tracking down response and resistance to TRK inhibitors. Cancer Discov. 2016;6(1):14-16. 5. Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023. 6. Kumar-Sinha C, Kalyana-Sundaram S, Chinnaiyan AM. Landscape of gene fusions in epithelial cancers: seq and ye shall find. Genome Med. 2015;7:129. doi:10.1186/s13073-015-0252-1. 7. Lange AM, Lo H-W. Inhibiting TRK proteins in clinical cancer therapy. Cancers. 2018;10(4):E105. doi:10.3390/cancers10040105. 8. Stransky N, Cerami E, Schalm S, Lim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846. doi:10.1038/ncomms5846. 9. Abel HJ, Al-Kateb H, Cottrell CE, et al. Detection of gene rearrangements in targeted clinical next-generation sequencing. J Mol Diagn. 2014;16(4):405-417. 10. Rogers T-M, Arnau GM, Ryland GL, et al. Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer. Sci Rep. 2017;7:42259. doi:10.1038/srep42259. 11. Hechtman JF, Benayed R, Hyman DM, et al. Pan-trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol. 2017;41(11):1547-1551. 12. Yan L, Zhang W. Precision medicine becomes reality—tumor type-agnostic therapy. Cancer Commun. 2018;38(1):6. doi:10.1186/s40880-018-0274-3. 13. Vendrell JA, Taviaux S, Béganton B, et al. Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches. Sci Rep. 2017;7(1):12510. doi:10.1038/s41598-017-12679-8.