A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer

Manuel Hidalgo, Elizabeth Bruckheimer, N. V. Rajeshkumar, Ignacio Garrido-Laguna, Elizabeth De Oliveira, Belen Rubio-Viqueira, Steven Strawn, Michael J. Wick, James Martell, David Sidransky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1311-1316
Number of pages6
JournalMolecular cancer therapeutics
Volume10
Issue number8
DOIs
StatePublished - Aug 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hidalgo, M., Bruckheimer, E., Rajeshkumar, N. V., Garrido-Laguna, I., De Oliveira, E., Rubio-Viqueira, B., Strawn, S., Wick, M. J., Martell, J., & Sidransky, D. (2011). A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer. Molecular cancer therapeutics, 10(8), 1311-1316. https://doi.org/10.1158/1535-7163.MCT-11-0233