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Substantial inter-patient variability exists within each subtype, resulting in markedly different clinical outcomes even among tumours of the same histological category. Proteomics provides a direct readout of tumour biology and pathway activity, complementing genomic information and enabling the identification of patient-specific actionable vulnerabilities. We applied a Total Protein Approach (TPA)-based prescriptomics framework that integrates absolute quantitative proteomics with curated drug\u2013target knowledge to nominate patient-specific drug-repurposing options, positioned as coadjuvants to the prevailing standard of care.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seventeen human kidney tissue specimens, seven clear cell RCC (ccRCC), five papillary RCC (pRCC), and five normal adjacent tissues (NAT), were retrieved from the publicly available PRIDE repository (PXD023296) and reanalysed by TPA-based absolute quantification applied to previously acquired label-free LC-MS\/MS data. Differential expression analysis between each tumour subtype and NAT identified subtype-specific upregulated proteins, wich were intersected with Therapeutic Target Database (TTD) to nominate FDA-approved drugs targeting dysregulated proteins as candidate repurposing strategies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ccRCC and pRCC produced distinct proteome-wide upregulation profiles consistent with their known biological drivers. TPA index stratification nominated bempedoic acid (ACLY inhibitor) and tipiracil hydrochloride (TYMP inhibitor) as patient-stratified candidates for ccRCC, and auranofin (TXNRD1 inhibitor), bempedoic acid, and mipomersen (APOB-directed antisense oligonucleotide) for pRCC. ACLY was the only top-priority target shared across both subtypes, pointing to a candidate cross-subtype metabolic vulnerability. Secondary candidates emerged from protein\u2013protein interaction network analysis in both subtypes..<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study presents a quantitative proteomics framework for translating individual-patient proteomic dysregulation into coadjuvant drug-repurposing hypotheses across the principal RCC subtypes. By combining the TPA for absolute protein quantification with prescriptomics-guided drug\u2013target mapping, we show that ccRCC and pRCC harbour distinct, individually stratifiable therapeutic vulnerabilities. These findings provide a proof-of-concept for proteomics-based treatment stratification in RCC and establish a scalable framework that, pending functional validation, could inform personalised therapeutic decision-making across RCC subtypes.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.17.738718","type":"posted-content","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:10:20Z","timestamp":1784311820000},"source":"Crossref","is-referenced-by-count":0,"title":["Absolute quantitative proteomics guides patient-stratified drug repurposing in clear cell and papillary renal cell carcinoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-4839","authenticated-orcid":false,"given":"Andr\u00e9 Q.","family":"Figueiredo","sequence":"first","affiliation":[{"name":"OMICS & Analytical Development and BIOSCOPE Research Group, LAQV REQUIMTE, Chemistry Department, NOVA School of Science and Technology, NOVA FCT, Portugal"},{"name":"PROTEOMASS Scientific Society, Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0757-657X","authenticated-orcid":false,"given":"In\u00eas F.","family":"Domingos","sequence":"additional","affiliation":[{"name":"OMICS & Analytical Development and BIOSCOPE Research Group, LAQV REQUIMTE, Chemistry Department, NOVA School of Science and Technology, NOVA FCT, Portugal"},{"name":"PROTEOMASS Scientific Society, Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-5446","authenticated-orcid":false,"given":"Carlos","family":"Lodeiro","sequence":"additional","affiliation":[{"name":"OMICS & Analytical Development and BIOSCOPE Research Group, LAQV REQUIMTE, Chemistry Department, NOVA School of Science and Technology, NOVA FCT, Portugal"},{"name":"PROTEOMASS Scientific Society, Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Dhir","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-8512","authenticated-orcid":false,"given":"Lu\u00eds B.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Proteomics Laboratory, Human Genetics Department, Instituto Nacional de Sa\u00fade Dr. Ricardo Jorge (INSA), Lisbon, Portugal"},{"name":"Comprehensive Health Research Centre (CHRC), NOVA Medical School, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0644-9461","authenticated-orcid":false,"given":"Laura","family":"Mercolini","sequence":"additional","affiliation":[{"name":"Group of Pharmaco-Toxicological Analysis (PTA Lab), Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum -University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-5095","authenticated-orcid":false,"given":"Jacek R.","family":"Wi\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-0105","authenticated-orcid":false,"given":"Gianluca","family":"Moroncini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy"},{"name":"Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, 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