Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies the Emergence of Drug-Tolerant Cancer Cells.
| Autor: | Celeste, Frank V., Powers, Scott |
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| Předmět: |
ADENOCARCINOMA
YAP signaling proteins DRUG resistance in cancer cells GENOMICS MELANOMA PROTEIN kinases CELL physiology CELLULAR signal transduction CELL lines LUNG tumors PROTEOMICS PHOSPHOLIPASES LUNG cancer STAT proteins EPIDERMAL growth factor receptors DRUG tolerance CONNECTIVE tissue growth factor |
| Zdroj: | Cancers; Mar2024, Vol. 16 Issue 5, p1001, 24p |
| Abstrakt: | Simple Summary: Targeted therapies are typically well tolerated and frequently lead to rapid tumor regression. However, the re-emergence of a drug-resistant tumors poses a significant challenge to their long-term effectiveness. A small subset of drug-tolerant "persister" cells have been identified as crucial precursors to full-fledged resistance. While various studies have pinpointed the activation of alternative signaling pathways as a key mechanism for evading therapy effects, targeting these secondary pathways alone has not yet reached the clinic. Currently, there is a pressing need for a more comprehensive profiling of the early drug-tolerant cellular landscape. This profiling is essential for understanding the underlying mechanisms driving resistance emergence and for devising more impactful therapeutic strategies. Drug resistance can evolve from a subpopulation of cancer cells that initially survive drug treatment and then gradually form a pool of drug-tolerant cells. Several studies have pinpointed the activation of a specific bypass pathway that appears to provide the critical therapeutic target for preventing drug tolerance. Here, we take a systems-biology approach, using proteomics and genomics to examine the development of drug tolerance to EGFR inhibitors in EGFR-mutant lung adenocarcinoma cells and BRAF inhibitors in BRAF-mutant melanoma cells. We found that there are numerous alternative mitogenic pathways that become activated in both cases, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC) pathways. Our results suggest that an effective therapeutic strategy to prevent drug tolerance will need to take multiple alternative mitogenic pathways into account rather than focusing on one specific pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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