Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation




Pharmacology and Nutritional Sciences

First Advisor

Dr. Rina Plattner


This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we reversed ERK1/2 reactivation and delayed proliferation of MEKi resistant cells both in vitro and in vivo. These findings suggest that ABL1/2 and DDR1 are potential therapeutic targets, and the combination of nilotinib with a MEK1/2 inhibitor may be a promising strategy for treating patients with refractory NRAS-driven melanomas.

Digital Object Identifier (DOI)

Funding Information

This study was supported by the following grants:

  • the Lloyd Charitable Trust from 2018-2021,
  • Markey Cancer Center Cancer Center Support Grant (CCSG) Pilot Award from 2018-2020,
  • Markey Cancer Foundation Women's Strong Award from 2017-2020 and 2023-2025, and
  • National Institute of Health/National Cancer Institute (no.: R01CA211137) from 2018-2024.

Available for download on Monday, May 11, 2026