Ex Vivo Drug Screening Informed Targeted Therapy for Metastatic Parotid Squamous Cell Carcinoma.

Noora Nykänen,Antti Arjonen,Juha K Rantala,Laura Lewandowski,Rainer Blaesius,Ville Härmä,Teijo Kuopio,Ismo Jantunen,Eileen Snowden,Rami Mäkelä,Juha Kononen

doi:10.3389/fonc.2021.735820

Abstract

The purpose of ex vivo drug screening in the context of precision oncology is to serve as a functional diagnostic method for therapy efficacy modeling directly on patient-derived tumor cells. Here, we report a case study using integrated multiomics ex vivo drug screening approach to assess therapy efficacy in a rare metastatic squamous cell carcinoma of the parotid gland. Tumor cells isolated from lymph node metastasis and distal subcutaneous metastasis were used for imaging-based single-cell resolution drug screening and reverse-phase protein array-based drug screening assays to inform the treatment strategy after standard therapeutic options had been exhausted. The drug targets discovered on the basis of the ex vivo measured drug efficacy were validated with histopathology, genomic profiling, and in vitro cell biology methods, and targeted treatments with durable clinical responses were achieved. These results demonstrate the use of serial ex vivo drug screening to inform adjuvant therapy options prior to and during treatment and highlight HER2 as a potential therapy target also in metastatic squamous cell carcinoma of the salivary glands.

Highlights

Ex vivo drug screening methods in the context of cancer research collectively refer to highthroughput screening (HTS) approaches that utilize vital patient-derived tumor cells as models for assessing drug efficacy
Treatment of the disease was initiated with cisplatin–5-fluorouracil chemotherapy regimen to reduce tumor burden
Parotid squamous cell carcinoma is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage with nodal metastases

Summary

Introduction

Ex vivo drug screening methods in the context of cancer research collectively refer to highthroughput screening (HTS) approaches that utilize vital patient-derived tumor cells as models for assessing drug efficacy. The utility of ex vivo drug screening has been pioneered in the context of hematological malignancies in which cancer cells can be collected and enriched for HTS directly from blood or bone marrow biopsies [7,8,9,10] These studies have demonstrated that the methods can be used to complement pathological cancer diagnostic procedures to track patient-specific drug sensitivity and guide treatment decisions on the most effective treatments or potential alternative therapies currently approved for other cancer indications. Clinical development of novel treatments to this malignancy is limited by the low number of cases, which limits the use of conventional clinical study designs Alternative approaches, such as the ex vivo screening, are needed to collect evidence on the efficacy of alternative targeted treatment strategies matched to the molecular characteristics of SCC tumors [17]

Methods

Results

Conclusion