Ex Vivo 2(star)2(star)2 Tumor Tissue Explant Culture for Precision Medicine in Immunotherapy and TKI progressors in Lung Cancer

S. Ghosh, M. Elkabets, K. Kundu, L. Roisman, D. Levitas, A. Porgador, N. Peled

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Background: Lung cancer is one of the leading causes of cancer
mortality worldwide. Despite of remarkable progress made in the lung
cancer therapy, an unmet need is there in tailoring the appropriate
patient specific therapy due to a variety of treatment options. Our aim
was to develop a high-throughput drug screening method of tumor exvivo analysis (TEVA) which can predict patient-specific drug response
and thus can be used for personalized cancer treatment. Method:
Freshly operated tumor tissue samples from non small cell lung carcinoma (NSCLC) patients were received from Soroka Medical Center,
Israel and implanted in NSG mice to form PDXs. We developed a
method that enabled us to cut the PDXs into 2*2*2mm tissue explants
and then treated with clinically relevant drugs (Genomics/proteomics
suggested) in 48 well plates for 24 hours. TMA blocks were prepared
and IHC was performed. Parameters, such as Ki67, TUNEL and
respective signalling molecules (pMAPK, pPRAS40) were chosen to
predict the drug response ex vivo and a score was given to each drug
based upon those parameters. Result: 8 NSCLC patients have been
enrolled so far. Implantation rate was 75%. 15 drugs combinations
have been developed to test the most common conditions, i.e. progression on EGFR TKIs, progression on immunotherapy and progression on chemotherapy. Preliminary results indicate a potential role for
MET blockade in immune-resistant as well as in EGFR progressors. We
also observed that the TEVA score correlated with the genomics/proteomics based drug results. Conclusion: Overall, this low cost, fast,
relatively simple and efficient method can bypass the necessity of drug
validation in mice and can be used for multiple drug screening to select
a precise patient specific drug. The method is feasible and expose ways
to overcome acquired resistant to novel drugs. Keywords: Immunotherapy, Tumor ex vivo analysis, TKIs
Original languageEnglish GB
Pages (from-to)S595-S595
JournalJournal of Thoracic Oncology
Volume13
Issue number10
StatePublished - Oct 2018

Keywords

  • Immunotherapy
  • Tumor ex vivo analysis
  • TKIs

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