Naslov
P53 in resistance to targeted therapy in metastatic melanoma

Autori
Radić, Martina ; Dekanić, Ana ; Jazvinšćak Jembrek, Maja ; Ozretić, Petar ; Herak Bosnar, Maja ; Slade, Neda

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
International p53/p63/p73 Isoforms Workshop, Book of Abstracts / Slade, Neda - Zagreb, 2019, 126-126

Skup
International p53/p63/p73 Isoforms Workshop

Mjesto i datum
Dubrovnik, Hrvatska, 03.11.2019. - 06.11.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
p53 isoforms ; metastatic melanoma ; treatment resistance ; vemurafenib

Sažetak
Malignant melanoma is the most aggressive form of skin cancer with increasing incidence. Recent advances in melanoma therapy that improve overall patient survival are held down by rapid and pervasive treatment resistance. Targeted therapy, like BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation, is initially highly effective, but a majority of the patients develop resistance and relapse within a few months. The tumor suppressor protein p53, mutated in more than 50% of human cancers, is rarely mutated in metastatic melanoma, but, nevertheless it fails to execute its tumor suppressor activity. To better understand the mechanisms of resistance to BRAFi targeted therapy, and to reveal the potential role of p53 isoforms in the process of acquisition of resistance, we generated vemurafenib-resistant metastatic melanoma cell lines by growing the A375M and WM793B cells in the vemurafenib-enriched medium and confirmed resistance by MTT assay. Vemurafenib is a BRAFi, used for the treatment of late-stage melanoma with the common BRAFV600E mutation. We analyzed the expression profile of p53 genes and proteins in control and resistant cell lines. Morphological change of newly generated resistant cell lines led us to test EMT (epithelial-mesenchymal transition) markers and we discovered partial EM transition. It is known that partial EMT increases invasive cell properties and promotes resistance to anti-cancer drugs. Furthermore, we determined transcriptional and quantitative gene expression by mass-based parallel cell mRNA sequencing (RNA-seq). The data obtained from RNA-seq showed that a mechanism of resistance differs between two cell lines. Activation of different signaling pathways presents promising results and sets up a path for further research.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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