Exploration of Targeted Anti-tumor Therapy

Table 3. Acquired resistance biomarkers to targeted therapy.

Study (n)	EGFR	BRAF	G12C	HER2
Harrold et al. [85] (n = 52)*	CIN (2, 3)	CIN (2, 3)	CIN (2, 3)	CIN (2, 3)
Parseghian et al. [86] (n = 569)*	EMT (1) ctDNA (MS)	NE	NE	NE
Woolston et al. [87] (n = 15)*	EMT (1)	NE	NE	NE
Du et al. [89] (n = 78)**	SIRT5 (2)	NE	NE	NE
Van den Bossche et al. [90]**	FAO (2)	NE	NE	NE
Kopetz et al. [83] (n = 318)*	NE	ctDNA (MS)	NE	NE
Shen et al. [91] **	NE	FAO (2)	NE	NE
Yaeger et al. [72] (n = 25)*	NE	NE	ctDNA	NE
Desai et al. [74] (n = 14)	NE	NE	ctDNA	NE
Viale et al. [93]**	NE	NE	OXPHOS (FAO) (2)	NE
Salgueiro et al. [98]**	NE	NE	CIN, cMET amp (2, 3)	NE
Parida et al. [96]**	NE	NE	NE	xCT (2)
Feng et al. [94]**	NE	NE	NE	FAO (2)

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CIN: chromosomal instability; MS: mutational signatures; ctDNA: circulating tumor DNA; amp: gene amplification; SIRT5: sirtuin 5; FAO: fatty acid oxidation; OXPHOS: oxidative phosphorylation; EMT: epithelial-mesenchymal transition; IMMETCOLS: immune-metabolic signature; xCT: cystine/glutamate antiporter (mechanism of ferroptosis resistance); NE: not evaluated. IMC1 (1), IMC2 (2), IMC3 (3): metabolic subtypes according to the IMMETCOLS classification. *: Clinical studies; **: preclinical studies. Most acquired mutations in RAS, BRAF, EGFR, and MAP2K1 were subclonal.

Declarations

Acknowledgments

Professional medical writing assistance was provided by Kevin Clayton.

Author contributions

MR: Writing—original draft, Writing—review & editing. MM: Supervision, Writing—original draft, Writing—review & editing. S Madurga: Supervision, Writing—review & editing. FEGV: Writing—original draft, Writing—review & editing. MAR: Writing—original draft, Writing—review & editing. S Marín: Supervision, Writing—review & editing. MC: Conceptualization, Supervision, Writing—review & editing. JM: Conceptualization, Supervision, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Joan Maurel, who is the Editorial Board Member of Exploration of Targeted Anti-tumor Therapy, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Both figures were created de novo by the authors using BioRender.com and do not reproduce or adapt material from previously published sources.

Funding

Authors acknowledge the support of MICIU/AEI/10.13039/501100011033/-European Commission FEDER funds [PID2023--150539OB-I00]; CIBER-EHD [EHD20PI03 and CB17/04/00023]; AC24/00028; AGAUR [2021-SGR-00350], and ICREA Foundation (ICREA Academia award). ARISTOS has received funding from the European Union’s Horizon Europe research and innovation programme under the Marie Sklodowska-Curie grant agreement No 101081334. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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