Exploration of Targeted Anti-tumor Therapy

Table 2. Distribution of key molecular alterations stratified by metastatic status.

Molecular variable	No. (%)	OM	PM	P
APC status
Wt	40 (31.5)	10	30	0.0250
Mut	87 (68.5)	40	47	0.0250
BRAF p.V600E status
Absent	118 (92.9)	49	69	0.0730
Present	9 (7.1)	1	8	0.0730
BRAF all mutations
Wt	115 (90.6)	47	68	0.2862
Mut	12 (9.4)	3	9	0.2862
ERBB2 amplification
Yes	10 (7.9)	2	8	0.1932
No	117 (92.1)	48	69	0.1932
PIK3CA status
Wt	92 (72.4)	35	57	0.6212
Mut	35 (27.6)	15	20	0.6212
RAS status
Wt	69 (54.3)	33	36	0.0341
Mut	58 (45.7)	17	41	0.0341
TP53 status
Wt	43 (33.9)	14	29	0.2628
Mut	84 (66.1)	36	48	0.2628
MSS
Stable	117 (92.1)	42	75	0.0064
Unstable	10 (7.9)	8	2	0.0064
TMB (mut/Mb)
≥ 10	35 (27.6)	19	16	0.0345
< 10	92 (72.4)	31	61	0.0345

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APC: adenomatous polyposis coli; BRAF: v-Raf murine sarcoma viral oncogene homolog B1; MSS: microsatellite stability; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RAS: Rat sarcoma viral oncogene family (including KRAS and NRAS); TMB: tumor mutational burden; TP53: tumor protein p53; OM: oligometastatic; PM: polymetastatic; ERBB2: v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2; Wt: wild-type.

Supplementary materials

The supplementary materials for this article are available at: https://www.explorationpub.com/uploads/Article/file/1002371_sup_1.pdf.

Declarations

Acknowledgments

We would like to express our gratitude to the TRIAL scientific association (CF: 92088670622) for their invaluable and unwavering collaboration on this work.

Author contributions

RS: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Writing—review & editing, Visualization. CP: Conceptualization, Methodology, Validation, Writing—review & editing. FS: Conceptualization, Validation, Data curation. NP: Conceptualization, Data curation, Writing—original draft. MC: Validation. MS: Validation. MI: Validation, Investigation. RR: Validation, Investigation. LC: Methodology, Validation. VG: Methodology, Investigation. GC: Methodology, Investigation. MB: Investigation. GS: Methodology, Validation, Writing—original draft, Supervision. AO: Conceptualization, Software, Formal analysis, Investigation, Resources, Writing—review & editing, Supervision, Funding acquisition. All authors read and approved the submitted version.

Conflicts of interest

Roberto Sirica, Nadia Petrillo, Monica Ianniello, Raffaella Ruggiero, Luisa Circelli, and Giovanni Savarese are employed by AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

The study was approved by the Institutional Review Board of Centro AMES under protocol no. CA03/2025. It was conducted in accordance with the principles of the Declaration of Helsinki and its subsequent amendments.

Consent to participate

Informed consent to participate in genetic testing in this study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

Raw sequencing data have been deposited in the European Nucleotide Archive (ENA) under the accession numbers reported at https://zenodo.org/records/18845198 (last accessed March 3, 2026).

Funding

This work was supported by grants from the Centro AMES, Centro Polidiagnostico Strumentale srl, 80013 Naples, Italy. Dr. Ottaiano is the recipient of a grant funded by the Italian Government, Ministry of Health (www.salute.gov.it; accessed on March 2, 2026), under the Ricerca Corrente L4/8 program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49. [DOI]

Capuozzo M, Picone C, Sabbatino F, Santorsola M, Caraglia F, Iervolino D, et al. Genetic, Epidemiological, Clinical, and Therapeutic Trajectories in Colon and Rectal Cancers. Cancers (Basel). 2025;17:3438. [DOI]

Cervantes A, Adam R, Roselló S, Arnold D, Normanno N, Taïeb J, et al.; ESMO Guidelines Committee. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34:10–32. [DOI]

Ottaiano A, Santorsola M, Circelli L, Trotta AM, Izzo F, Perri F, et al. Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives. Cancers (Basel). 2023;15:1827. [DOI]

Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, et al. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiother Oncol. 2020;148:157–66. [DOI]

Sonkin D, Thomas A, Teicher BA. Cancer treatments: Past, present, and future. Cancer Genet. 2024;286–287:18–24. [DOI]

Ottaiano A, Nasti G, Santorsola M, Altieri V, Di Fruscio G, Circelli L, et al. KRAS Mutational Regression Is Associated With Oligo-Metastatic Status and Good Prognosis in Metastatic Colorectal Cancer. Front Oncol. 2021;11:632962. [DOI]

Ottaiano A, de Vera d’Aragona RP, Trotta AM, Santorsola M, Napolitano M, Scognamiglio G, et al. Characterization of KRAS Mutational Regression in Oligometastatic Patients. Front Immunol. 2022;13:898561. [DOI]

Gatenby RA, Brown JS. Integrating evolutionary dynamics into cancer therapy. Nat Rev Clin Oncol. 2020;17:675–86. [DOI]

10.

Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011;8:378–82. [DOI] [PubMed]

11.

Ray SK, Mukherjee S. Exploring replication stress and cellular senescence as key targets in novel cancer therapies. Cancer Genet. 2025;298–299:78–87. [DOI] [PubMed]

12.

Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422. [DOI] [PubMed]

13.

Martin L, Senesse P, Gioulbasanis I, Antoun S, Bozzetti F, Deans C, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2015;33:90–9. [DOI] [PubMed]

14.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47. [DOI] [PubMed]

15.

Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9:34. [DOI] [PubMed] [PMC]

16.

Cortes-Ciriano I, Lee S, Park WY, Kim TM, Park PJ. A molecular portrait of microsatellite instability across multiple cancers. Nat Commun. 2017;8:15180. [DOI] [PubMed] [PMC]

17.

Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60. [DOI] [PubMed] [PMC]

18.

Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19:4–23. [DOI] [PubMed] [PMC]

19.

Li MM, Cottrell CE, Pullambhatla M, Roy S, Temple-Smolkin RL, Turner SA, et al. Assessments of Somatic Variant Classification Using the Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists Guidelines: A Report from the Association for Molecular Pathology. J Mol Diagn. 2023;25:69–86. [DOI] [PubMed]

20.

Palmeri M, Mehnert J, Silk AW, Jabbour SK, Ganesan S, Popli P, et al. Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers. ESMO Open. 2022;7:100336. [DOI] [PubMed] [PMC]

21.

Yang H, Robinson PN, Wang K. Phenolyzer: phenotype-based prioritization of candidate genes for human diseases. Nat Methods. 2015;12:841–3. [DOI] [PubMed] [PMC]

22.

Xu T, Li J, Wang Z, Zhang X, Zhou J, Lu Z, et al. Real-world treatment and outcomes of patients with metastatic BRAF mutant colorectal cancer. Cancer Med. 2023;12:10473–84. [DOI] [PubMed] [PMC]

23.

Wilbur HC, Le DT, Agarwal P. Immunotherapy of MSI Cancer: Facts and Hopes. Clin Cancer Res. 2024;30:1438–47. [DOI] [PubMed]

24.

Wang Q, Yu M, Zhang S. The characteristics of the tumor immune microenvironment in colorectal cancer with different MSI status and current therapeutic strategies. Front Immunol. 2025;15:1440830. [DOI] [PubMed] [PMC]

25.

Zhang J, Xu Y, Han X, Gao Y, Wei Z, Sun X. Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype. Cancer Genet. 2025;298–299:141–50. [DOI] [PubMed]

26.

Jahangiri L. The impact of extracellular vesicles on breast cancer metastasis and therapeutics: genetic considerations. Cancer Genet. 2025;298–299:1–9. [DOI] [PubMed]

27.

Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 2008;8:193–204. [DOI] [PubMed]

28.

de Almeida LC, Calil FA, Machado-Neto JA, Costa-Lotufo LV. DNA damaging agents and DNA repair: From carcinogenesis to cancer therapy. Cancer Genet. 2021;252–253:6–24. [DOI] [PubMed]

29.

Chen H, Chong W, Wu Q, Yao Y, Mao M, Wang X. Association of LRP1B Mutation With Tumor Mutation Burden and Outcomes in Melanoma and Non-small Cell Lung Cancer Patients Treated With Immune Check-Point Blockades. Front Immunol. 2019;10:1113. [DOI] [PubMed] [PMC]

30.

He Z, Feng W, Wang Y, Shi L, Gong Y, Shi Y, et al. LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors. Transl Lung Cancer Res. 2023;12:510–29. [DOI] [PubMed] [PMC]

31.

Tan S, Chen Y, Chen Y, Liu S, Yang C, Mi Y, et al. HOXC8-activated TRIM22/NF-κB pathway promotes stemness in colorectal cancer. Cancer Lett. 2026;638:218156. [DOI] [PubMed]

32.

Liu H, Guo Z, Wang P. Genetic expression in cancer research: Challenges and complexity. Gene Rep. 2024;37:102042. [DOI]

33.

Liu H, Li Y, Karsidag M, Tu T, Wang P. Technical and Biological Biases in Bulk Transcriptomic Data Mining for Cancer Research. J Cancer. 2025;16:34–43. [DOI] [PubMed] [PMC]

34.

Liu H. A prospective for the potential effect of local anesthetics on stem-like cells in colon cancer. Biomed J Sci Tech Res. 2020;25. [DOI]