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Page 998 Juhlin. Cancer Drug Resist 2020;3:992-1000 I http://dx.doi.org/10.20517/cdr.2020.66

ATCs are feared tumors in the clinical setting, not least due to the limited response to conventional
[2,6]
treatment options . The advent of molecular testing has helped identify subset of tumors with potentially
targetable mutations, not least mutations in BRAF, mTOR, and ERBB2. Even though partial responses
have been noted, exceedingly few patients survive once the tumor spreads to distant sites [13,14] . The notion
that a proportion of ATCs exhibit MMR deficiency should therefore not be overlooked, as MMR deficient
tumors could mandate specific therapeutic considerations, and as the hypermutability in turn might give
[44]
rise to additional targetable mutations . Especially the promising value of immune checkpoint inhibitors
in subsets of ATCs should be evaluated against the MMR status of these tumors, as the hypermutability
in MMR deficient ATCs in theory would generate a massive overrepresentation of “non-self” tumoral
antigens, in turn priming the patient’s immune response. However, as most ATCs lack hypermutability and
MMR deficiency, the identification of additional molecular mechanisms suitable for targeted therapies is
still highly warranted for the majority of cases.

To conclude, ATC patient outcome is exceedingly poor when distant spread is evident. While conventional
treatment options are largely ineffective, targeted molecular therapy has shown promising results in terms
of prolonged survival even after disease dissemination. The knowledge that subsets of ATCs probably arise
as a clonal evolution from DNA repair malfunctioning precursor tumors could potentially be of importance
when considering adjuvant treatment options for this ill-fated patient category, not least through direct or
indirect targeting of a defective MMR system.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by the Swedish Cancer Society (Junior Clinical Investigator Award).

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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