scholarly journals Microphthalmia‐associated transcription factor in melanoma development and MAP ‐kinase pathway targeted therapy

2015 ◽  
Vol 28 (4) ◽  
pp. 390-406 ◽  
Author(s):  
Claudia Wellbrock ◽  
Imanol Arozarena
2019 ◽  
Author(s):  
Margaux Sala ◽  
Nathalie Allain ◽  
Elodie Henriet ◽  
Arnaud Uguen ◽  
Sylvaine Di-Tommaso ◽  
...  

AbstractAnti-BRAF plus an anti-MEK is currently used in first line for the management of patients presenting metastatic melanomas harboring the BRAF V600E mutation. However, the main issue during targeted therapy is the acquisition of cellular resistance in 80% of the patients, which is associated with an increased metastasis due to the hyperactivation of MAP kinase pathway. Previous reports have indicated that Discoidin Domain Receptors (DDRs) 1 and 2 can activate this pathway. To study the role of DDRs in melanoma cell resistance to targeted therapy, we first determined that DDRs are overexpressed in vemurafenib resistant cells compared to sensitive cells. We demonstrated that DDRs depletion or inactivation by DDRs inhibitors such as dasatinib or CR-13542 reduces tumor cell proliferation, due to a decrease of MAP kinase pathway activity in resistant cells. Finally, we confirmed these results in vivo in a xenograft mouse model and show that DDRs could be new therapeutic targets in resistant patients with metastatic melanoma. We propose that dasatinib could be a second-line treatment after the bi-therapy in resistant patients overexpressing DDRs.


1996 ◽  
Vol 10 (18) ◽  
pp. 2289-2301 ◽  
Author(s):  
M G Wilkinson ◽  
M Samuels ◽  
T Takeda ◽  
W M Toone ◽  
J C Shieh ◽  
...  

2021 ◽  
Vol 28 (5) ◽  
pp. 3978-3986
Author(s):  
Rodrigo Rigo ◽  
Jordan Doherty ◽  
Kim Koczka ◽  
Shiying Kong ◽  
Philip Q. Ding ◽  
...  

Immune checkpoint and MAP kinase pathway inhibitors can significantly improve long-term survival for patients with melanoma. There is limited real-world data of these regimens’ effectiveness. We retrospectively analyzed 402 patients with unresectable and metastatic melanoma between August 2013 and July 2020 treated with immune checkpoint inhibitors and MAP kinase pathway targeted therapy in Alberta, Canada. Overall survival (OS) was compared using Kaplan–Meier and Cox regression analyses. Subgroup survival outcomes were analyzed by first-line treatment regime and BRAF mutation status. Three treatment eras were defined based on drug access: prior to August 2013, August 2013 to November 2016, and November 2016 to July 2020. Across each era, there were improvements in median OS: 11.7 months, 15.9 months, and 33.6 months, respectively. Patients with BRAF mutant melanoma had improved median OS when they were treated with immunotherapy in the first line as opposed to targeted therapy (median OS not reached for immunotherapy versus 17.4 months with targeted treatment). Patients with BRAF wild-type melanomas had improved survival with ipilimumab and nivolumab versus those treated with a single-agent PD-1 inhibitor (median OS not reached and 21.2 months). Our real-world analysis confirms significant survival improvements with each subsequent introduction of novel therapies for advanced melanoma.


2005 ◽  
Vol 173 (4S) ◽  
pp. 157-158
Author(s):  
Rono Mukherjee ◽  
Sarath K. Nalagatla ◽  
Mark A. Undenvood ◽  
John M.S. Bartlett ◽  
Joanne Edwards

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