Retsevmo ® (selperkatinib)

För fullständig produktresumé för Retsevmo se FASS.

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Retsevmo® ▼ (selperkatinib): Översikt av RET-tyrosinkinasreceptorn

RET-tyrosinkinasreceptorn har en kritisk roll i normal utveckling av njur- och enterosystemet, och för underhåll av flera vävnadstyper hos vuxna.

Detailed Information

The RET RTK has critical roles in normal kidney and enteric nervous system development and in the maintenance of several adult tissue types, including

  • neural

  • neuroendocrine

  • hematopoietic, and

  • male germ cell tissues.1

The RET RTK is the receptor for ligands belonging to the GFL. The GFL are composed of GDNF, neurturin, persephin, and artemin. These ligands are not able to bind RET on their own, but require a ligand-binding subunit acting as a co-receptor, known as GFRα co-receptors. During RET activation, the GFL bind to 4 different GFRα co-receptors.1

The GFL–GFRα complex induces RET homodimerization, which activates intracellular kinase domains. This action results in RET receptor autophosphorylation and subsequent downstream activation of signal transduction pathways responsible for

  • cell growth

  • survival

  • differentiation, and

  • proliferation.1

RET can be altered by 2 primary mechanisms

  • chromosomal rearrangements that fuse the RET kinase domain with a partner protein dimerization domain producing hybrid proteins with ligand-independent activity,2-5 or

  • point mutations that directly or indirectly activate the RET kinase.6-8

Genetic alterations in the RET gene are implicated in the pathogenesis of several human cancers. For RET, fusions and mutations are the key alterations.7 The term RET-altered cancers encompasses RET-fusions and RET-mutations, as described in Table 1.

Table 1. RET-Altered Cancers1,9,10





Genomic abnormalities that occur when the RET gene becomes fused with another unrelated gene.
The hybrid gene no longer functions normally, which can lead to an overproduction of abnormal RET proteins that are turned on all of the time, leading to uncontrolled cell growth.

Genomic abnormalities that occur when a small change in the RET gene alters the function of the protein, causing uncontrolled cell growth.

Most common alterations

  • KIF5B in lung cancer

  • CCDC6 and NCOA4 in thyroid cancer



  • 2% of NSCLC

  • 10-20% of papillary and other thyroid cancers

  • 1% of pancreatic cancer, salivary gland cancer, Spitz cancer, CRC, ovarian cancer, myeloproliferative disorder

Appears to be limited to MTC, with approximately

  • >60% in sporadic MTC, and

  • >90% in hereditary MTC.

Abbreviations: CCDC6 = coiled-coil domain containing 6; CRC = colorectal cancer; KIF5B = kinesin family member 5B; MTC = medullary thyroid cancer; NCOA4 = nuclear receptor coactivator 4; NSCLC = non-small cell lung cancer; RET = rearranged during transfection.

Figure 1. A detailed visual representation of the mechanism of disease of RET-altered cancers may be accessed by clicking here


1. Drilon A, Hu ZI, Lai GG, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167.

2. Romei C, Ciampi R, Elisei, R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol. 2016;12(4):192-202.

3. Kohno T, Ichikawa H, Totoki Y, et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012;18(3):375-377.

4. Takeuchi K, Soda M, Togashi Y, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012;18(3):378-381.

5. Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18(3):382-384.

6. Donis-Keller H, Dou S, Chi D, et al. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet. 1993;2(7):851-856.

7. Mulligan LM, Kwok JB, Healey CS, et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363(6428):458-460.

8. Hofstra RM, Landsvater I, Ceccherini I, et al. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature. 1994;367(6461):375-376.

9. Pietrantonio F, Di Nicolantonio F, Schrock AB, et al. RET fusions in a small subset of advanced colorectal cancers at risk of being neglected. Ann Oncol. 2018;29(6):1394-1401.

10. Su X, He C, Ma J, et al. RET/PTC rearrangements are associated with elevated postoperative TSH levels and multifocal lesions in papillary thyroid cancer without concomitant thyroid benign disease. PLoS One. 2016;11(11):e0165596.


GDNF = glial cell derived neurotrophic factor

GFL = glial cell derived neurotrophic factor family ligands

GFRα = glial cell derived neurotrophic factor family receptor alpha

RET = rearranged during transfection

RTK = receptor tyrosine kinase

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn January 22, 2021

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