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Drug Res (Stuttg) 2019; 69(09): 512-518
DOI: 10.1055/a-0873-3529
Opinion Paper
© Georg Thieme Verlag KG Stuttgart · New York

A Cautious Note on Thalidomide Usage in Cancer Treatment: Genetic Profiling of the TBX2 Sub-Family Gene Expression is Required

Georges Nemer
1   Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
,
Athar Khalil
1   Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
› Author Affiliations
Further Information

Publication History

received 09 December 2018

accepted 05 March 2019

Publication Date:
01 April 2019 (online)

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Abstract

Thalidomide is still by excellence the mysterious drug that fascinated, blurred, misled, and changed the scientific community perspectives and policies. It was introduced in the 1950’s as a sedative drug, then shortly withdrawn because of the devastating birth defects that affected tens of thousands throughout more than 40 countries. Back into the market in the mid 1990’s and 2000’s the drug is now being used to treat skin immune-related conditions and some cancers like multiple myeloma. Despite numerous beneficial effects which led to the development of new analogs, its direct mechanisms of action are still elusive. The identification of CRBN and TBX5 as potential direct ligands for this drug have opened the way to better understand its efficiency and its failure.

We hereby review these mechanisms and provide evidence that could explain why thalidomide failed to make it as a drug of choice in lung cancer treatment. Linking the genetic signature of TBX2 subfamily in these tumors to their inability to respond properly to thalidomide raises concerns of worsening lung cancer patients’ health if this drug is utilized.

Key words

thalidomide - TBX2 - clinical trials - lung, cancer
 

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