CUSP9 [Coordinated Undermining of Survival Paths] is one of several cancer treatment protocols using re-purposed older drugs to interfere with cancer cell's growth signaling rather than directly killing them with cytotoxic drugs. CUSP9 is a treatment specifically targeted to glioblastoma that adds to a traditional cancer cell killing drug, temozolomide, nine older, non-cytotoxic drugs to block growth factors that enhance or drive glioblastoma growth [aprepitant blocks NK-1, auranofin inhibits thioredoxin reductase, captopril inhibits angiotensin converting enzyme, celecoxib blocks cyclooxygenase-2, disulfiram blocks aldehyde dehydrogenase, itraconazole blocks Hedgehog signaling, minocycline inhibits metalloproteinase-2 and -9, quetiapine inhibits RANKL, sertraline inhibits Tissue Factor]. These targets have been shown to be active in glioblastoma.
CUSP9 is related several other trials using a similar conceptual approach: The COMBAT regimen  for treating various advanced pediatric cancers that uses two re-purposed non-cytotoxic drugs to augment two traditional cytotoxic drugs, or the GLAD regimen that uses one traditional anti-cancer drug, gefitinib, with three re-purposed non-cancer drugs. Or the MEMMAT regimen, in a current trial of A.Peyrl et al. using a 7 drug cocktail, (ClinicalTrials.gov Identifier: NCT01356290)- non-cytotoxic drugs bevacizumab, thalidomide, celecoxib, and fenofibric acid to augment traditional cytotoxic drugs etoposide, cyclophosphamide, and cytarabine to treat progressive medulloblastoma.
The ReDO project and many others  also follow this line of thought as in CUSP9 - repurposing older drugs for their anti-cancer effect and simultaneous use of several of them] in cancer treatment.
None of these treatment regimens have been proven to be safe or effective in human cancers but are occasionally tried on compassionate-use basis in patients who have exhausted all other options. A formal trial of the CUSP9 protocol in recurrent glioblastoma [ClinicalTrials.gov Identifier: NCT02770378] is starting in Ulm, Germany.
- CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide. Oncotarget. 2014;5(18):8052-82. PMID 25211298.
- A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care. Oncotarget. 2013;4(4):502-30. PMID 23594434; PMC 3720600.
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- Multitargeted low-dose GLAD combination chemoprevention: a novel and promising approach to combat colon carcinogenesis. Neoplasia. 2013;15(5):481-90. PMID 23633920; PMC 3638351.
- Pantziarka P, Bouche G, Meheus L, Sukhatme V, Sukhatme VP, Vikas P. The Repurposing Drugs in Oncology (ReDO) Project. ecancermedicalscience. 2014;8:442. doi:10.3332/ecancer.2014.442.
- "CUSP9*, 9 nine repurposed drugs, glioblastoma, temozolomide - Anticancer Fund". anticancerfund.org.
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