title: A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer.
abstract: Patients with many advanced solid cancers have very poor prognosis, and improvements in life expectancy are measured only in months. We have recently reported the remarkable clinical outcome of a patient with advanced, gemcitabine-resistant, pancreatic cancer who was later treated with DNA-damaging agents, on the basis of the observation of significant activity of this class of drugs against a personalized tumorgraft generated from the patient's surgically resected tumor. Here, we extend the approach to patients with other advanced cancers. Tumors resected from 14 patients with refractory advanced cancers were propagated in immunodeficient mice and treated with 63 drugs in 232 treatment regimens. An effective treatment regimen in the xenograft model was identified for 12 patients. One patient died before receiving treatment, and the remaining 11 patients received 17 prospectively guided treatments. Fifteen of these treatments resulted in durable partial remissions. In 2 subjects, no effective treatments were found. Overall, there was a remarkable correlation between drug activity in the model and clinical outcome, both in terms of resistance and sensitivity. The data support the use of the personalized tumorgraft model as a powerful investigational platform for therapeutic decision making and to efficiently guide cancer treatment in the clinic.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. mhidalgo@cnio.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bruckheimer
authors.forename: N V
authors.initials: NV
authors.lastname: Rajeshkumar
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garrido-Laguna
authors.forename: Elizabeth
authors.initials: E
authors.lastname: De Oliveira
authors.forename: Belen
authors.initials: B
authors.lastname: Rubio-Viqueira
authors.forename: Steven
authors.initials: S
authors.lastname: Strawn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wick
authors.forename: James
authors.initials: J
authors.lastname: Martell
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010597:Pharmacogenetics; D010865:Pilot Projects; D057285:Precision Medicine; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents