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Involvement of the AKT pathway in resistance to erlotinib and cabozantinib in triple negative breast cancer cell lines.

ABSTRACT: Resistance to tyrosine kinase inhibitors (TKIs) presents a growing challenge in the development of therapeutic targets for cancers such as triple negative breast cancer (TNBC), where conventional therapies are ineffective for combatting systemic disease. Due to increased expression, the receptor tyrosine kinases EGFR (epidermal growth factor receptor) and c-Met are potential targets for treatment. However, targeted anti-EGFR and anti-c-Met therapies have faced mixed results in clinical trials due to acquired resistance. We hypothesize that the upregulation of kinases within the EGFR and c-Met signaling axes contribute to the development of acquired erlotinib and cabozantinib resistance. To test this, we developed two separate models for cabozantinib and erlotinib resistance using the MDA-MB-231 and MDA-MB-468 cell lines, respectively. With a SILAC (Stable Isotope Labeling of Amino acids in Cell Cul-ture)-labeled quantitative mass spectrometry proteomics approach, we assessed the effects of erlotinib- or cabozantinib resistance on the phosphoproteome, proteome and kinome. Using this integrated proteomics approach, we identified several potential kinase mediators of cabozan-tinib-resistance and confirmed the contribution of AKT1 to erlotinib-resistance in TNBC resistant cell lines.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Dr. Alison Allan

PROVIDER: PXD043368 | JPOST Repository | Fri Jun 28 00:00:00 BST 2024

REPOSITORIES: jPOST

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			Action	DRS
	231_Phospho_RAWfiles.zip	Other
	231_Proteome_RAWfiles.zip	Other
	468_Proteome_RAWfiles.zip	Other
	NBCC00062_20210622_Allan_Cory_Kinome_MDAMB231_S_Light_LR_M_IP7_half.raw	Raw
	NBCC00062_20210622_Allan_Cory_Kinome_MDAMB231_S_Light_LR_M_IP8_all.raw	Raw

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