NRAS mutant melanoma: towards better therapies
Genetic alterations affecting RAS proteins are commonly found in human cancers. Roughly a fourth of melanoma patients carry activating NRAS mutations, rendering this malignancy particularly challenging to treat. Although the development of targeted as well as immunotherapies led to a substantial imp...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
September 2021
|
| In: |
Cancer treatment reviews
Year: 2021, Volume: 99, Pages: 1-12 |
| ISSN: | 1532-1967 |
| DOI: | 10.1016/j.ctrv.2021.102238 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ctrv.2021.102238 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0305737221000864 
|
| Author Notes: | Tijana Randic, Ines Kozar, Christiane Margue, Jochen Utikal, Stephanie Kreis |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1833030656 | ||
| 003 | DE-627 | ||
| 005 | 20230707010642.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230202s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ctrv.2021.102238 |2 doi | |
| 035 | |a (DE-627)1833030656 | ||
| 035 | |a (DE-599)KXP1833030656 | ||
| 035 | |a (OCoLC)1389536581 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Randic, Tijana |e VerfasserIn |0 (DE-588)1279824360 |0 (DE-627)1833030591 |4 aut | |
| 245 | 1 | 0 | |a NRAS mutant melanoma |b towards better therapies |c Tijana Randic, Ines Kozar, Christiane Margue, Jochen Utikal, Stephanie Kreis |
| 264 | 1 | |c September 2021 | |
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 02.02.2023 | ||
| 520 | |a Genetic alterations affecting RAS proteins are commonly found in human cancers. Roughly a fourth of melanoma patients carry activating NRAS mutations, rendering this malignancy particularly challenging to treat. Although the development of targeted as well as immunotherapies led to a substantial improvement in the overall survival of non-NRASmut melanoma patients (e.g. BRAFmut), patients with NRASmut melanomas have an overall poorer prognosis due to the high aggressiveness of RASmut tumors, lack of efficient targeted therapies or rapidly emerging resistance to existing treatments. Understanding how NRAS-driven melanomas develop therapy resistance by maintaining cell cycle progression and survival is crucial to develop more effective and specific treatments for this group of melanoma patients. In this review, we provide an updated summary of currently available therapeutic options for NRASmut melanoma patients with a focus on combined inhibition of MAPK signaling and CDK4/6-driven cell cycle progression and mechanisms of the inevitably developing resistance to these treatments. We conclude with an outlook on the most promising novel therapeutic approaches for melanoma patients with constitutively active NRAS. - Statement of significance - An estimated 75000 patients are affected by NRASmut melanoma each year and these patients still have a shorter progression-free survival than BRAFmut melanomas. Both intrinsic and acquired resistance occur in NRAS-driven melanomas once treated with single or combined targeted therapies involving MAPK and CDK4/6 inhibitors and/or checkpoint inhibiting immunotherapy. Oncolytic viruses, mRNA-based vaccinations, as well as targeted triple-agent therapy are promising alternatives, which could soon contribute to improved progression-free survival of the NRASmut melanoma patient group. | ||
| 650 | 4 | |a Cutaneous melanoma | |
| 650 | 4 | |a MEKi/CDK4/6i dual therapy | |
| 650 | 4 | |a mutation | |
| 650 | 4 | |a New combination therapies | |
| 650 | 4 | |a Resistance mechanisms | |
| 700 | 1 | |a Kozar, Ines |e VerfasserIn |4 aut | |
| 700 | 1 | |a Margue, Christiane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Utikal, Jochen |d 1974- |e VerfasserIn |0 (DE-588)1026463750 |0 (DE-627)726765015 |0 (DE-576)371816580 |4 aut | |
| 700 | 1 | |a Kreis, Stephanie |e VerfasserIn |0 (DE-588)1163735124 |0 (DE-627)1028098820 |0 (DE-576)508180384 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer treatment reviews |d Amsterdam [u.a.] : Elsevier, 1974 |g 99(2021) vom: Sept., Artikel-ID 102238, Seite 1-12 |h Online-Ressource |w (DE-627)320417158 |w (DE-600)2002084-3 |w (DE-576)104194154 |x 1532-1967 |7 nnas |a NRAS mutant melanoma towards better therapies |
| 773 | 1 | 8 | |g volume:99 |g year:2021 |g month:09 |g elocationid:102238 |g pages:1-12 |g extent:12 |a NRAS mutant melanoma towards better therapies |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.ctrv.2021.102238 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0305737221000864 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230202 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 1026463750 |a Utikal, Jochen |m 1026463750:Utikal, Jochen |d 60000 |e 60000PU1026463750 |k 0/60000/ |p 4 | ||
| 999 | |a KXP-PPN1833030656 |e 4262716384 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"note":["Gesehen am 02.02.2023"],"recId":"1833030656","id":{"eki":["1833030656"],"doi":["10.1016/j.ctrv.2021.102238"]},"title":[{"subtitle":"towards better therapies","title":"NRAS mutant melanoma","title_sort":"NRAS mutant melanoma"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedDisp":"September 2021","dateIssuedKey":"2021"}],"language":["eng"],"relHost":[{"pubHistory":["1.1974 -"],"recId":"320417158","note":["Gesehen am 22.01.2020"],"disp":"NRAS mutant melanoma towards better therapiesCancer treatment reviews","id":{"issn":["1532-1967"],"eki":["320417158"],"zdb":["2002084-3"]},"title":[{"title_sort":"Cancer treatment reviews","title":"Cancer treatment reviews"}],"physDesc":[{"extent":"Online-Ressource"}],"part":{"text":"99(2021) vom: Sept., Artikel-ID 102238, Seite 1-12","volume":"99","extent":"12","year":"2021","pages":"1-12"},"type":{"media":"Online-Ressource","bibl":"periodical"},"origin":[{"publisher":"Elsevier ; Harcourt","dateIssuedDisp":"1974-","dateIssuedKey":"1974","publisherPlace":"Amsterdam [u.a.] ; Burlington, Mass."}],"language":["eng"]}],"person":[{"family":"Randic","roleDisplay":"VerfasserIn","display":"Randic, Tijana","role":"aut","given":"Tijana"},{"given":"Ines","display":"Kozar, Ines","role":"aut","family":"Kozar","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","family":"Margue","given":"Christiane","role":"aut","display":"Margue, Christiane"},{"role":"aut","display":"Utikal, Jochen","given":"Jochen","family":"Utikal","roleDisplay":"VerfasserIn"},{"given":"Stephanie","display":"Kreis, Stephanie","role":"aut","family":"Kreis","roleDisplay":"VerfasserIn"}],"name":{"displayForm":["Tijana Randic, Ines Kozar, Christiane Margue, Jochen Utikal, Stephanie Kreis"]},"physDesc":[{"extent":"12 S."}]} | ||
| SRT | |a RANDICTIJANRASMUTANT2021 | ||