Reactions 1680, p101 - 2 Dec 2017
Development of acquired resistance due to acquired
PIK3CA gene mutation: case report
An elderly woman in her 60s [specific age at the time of
reaction onset not stated] developed acquired resistance to
crizotinib due to acquired PIK3CA gene mutation during
treatment for lung adenocarcinoma [dosage and outcome not
The woman was diagnosed with stage IIIB lung
adenocarcinoma, on 13 April 2015. Subsequently, she
received chemotherapy with various drugs including
pemetrexed, carboplatin and bevacizumab. A CT scan revealed
progression of the pulmonary lesions, on 20 November 2015.
A next generation sequencing was performed on her blood
sample, which demonstrated CD74-ROS1 fusion, a variant of
the ROS1 translocation, and C176F and G245S mutation in
TP53 gene. She was started on oral crizotinib, on
20 January 2016. A repeated CT scan showed a partial
response of her pulmonary lesions, on 03 March 2016.
However, she experienced chest tightness and shortness of
breath, in June 2016. A CT scan performed on 08 July 2016
demonstrated rapid progression of the pulmonary lesions
indicative of an acquired resistance to crizotinib. A subsequent
next generation sequencing was performed on her blood
samples, which revealed a novel point mutation of L531P type
of the PIK3CA gene. The novel point mutation of the PIK3CA
gene activated the mTOR signalling pathway.
Considering this activation, the woman was treated with
everolimus. However, disease progression was substantially
significant by this time. She eventually died due to circulatory
failure on 16 August 2016.
Author comment: "The patient reported herein was
diagnosed with lung adenocarcinoma and harbored a ROS1
rearrangement. She initially showed a response to crizotinib
treatment, but the disease ultimately progressed. We
identified an acquired mutation in her blood that led to
mTOR pathway activation, which conferred resistance to
Xu C-W, et al. Patient harboring a novel PIK3CA point mutation after acquired
resistance to crizotinib in an adenocarcinoma with ROS1 rearrangement: A case
report and literature review. Thoracic Cancer 8: 714-719, No. 6, Nov 2017.
Available from: URL: http://doi.org/10.1111/1759-7714.12496 - China
Reactions 2 Dec 2017 No. 16800114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved