Science Forum: Challenges in validating candidate therapeutic targets in cancer

  1. Jeffrey Settleman  Is a corresponding author
  2. Charles L Sawyers
  3. Tony Hunter
  1. Calico Life Sciences, United States
  2. Memorial Sloan Kettering Cancer Center, United States
  3. Salk Institute for Biological Studies, United States
1 table

Tables

Table 1
Articles suggesting a link between MELK and human cancers.

The 33 articles listed in column 1 of this table suggest that MELK has a role in a variety of human cancers, which makes in a candidate therapeutic target for cancer drugs. Columns 2–5 indicate which articles reported certain kinds of evidence to make the link between MELK and cancer, column 6 indicates the studies that used a MELK inhibitor called OTS167 (which is currently undergoing clinical trials). However, three recent papers (Lin et al., 2017; Huang et al., 2017; Giuliano et al., 2018) suggest that MELK should not be considered as a candidate therapeutic target.

https://doi.org/10.7554/eLife.32402.002
Articles reporting that MELK expression is up-regulated in various human cancersArticles reporting an association between increased MELK expression and poor clinical prognosisArticles reporting efficacy of MELK-targeted RNAi in cancer cell lines and/or xenograft tumor modelsArticles reporting efficacy with small-molecule inhibitors of MELK in cancer cell lines and/or xenograft tumor modelsArticles that made use of the MELK inhibitor OTS167 (also known as OTSSP167)
Gray et al. (2005)xx
Lin et al. (2007)xx
Marie et al. (2008)xxx
Nakano et al. (2008)xxx
Nakano et al. (2009)xx
Pickard et al. (2009)xxx
Hebbard et al. (2010)x
Choi and Ku (2011)x
Chung et al. (2012)xx
Gu et al. (2013)xxx
Kuner et al. (2013)xx
Minata et al. (2014)xx
Wang et al. (2014)xxxx
Du et al. (2014)xxx
Alachkar et al. (2014)xxxxx
Beke et al. (2015)x
Li et al. (2016)xxxxx
Inoue et al. (2016)xxxx
Chung et al. (2016)xx
Kato et al. (2016)xx
Touré et al., 2016xx
Wang et al. (2016)xxx
Stefka et al. (2016)xx
Xia et al. (2016)xxx
Speers et al., 2016xxxxx
Hiwatashi et al., 2016xx
Kohler et al. (2017)xxxx
Simon et al. (2017)xxx
Edupuganti et al. (2017)x
Liu et al., 2017xxxxx
Matsuda et al. (2017)x
Bolomsky et al., 2017xxxx
Janostiak et al., 2017xxxxx

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  1. Jeffrey Settleman
  2. Charles L Sawyers
  3. Tony Hunter
(2018)
Science Forum: Challenges in validating candidate therapeutic targets in cancer
eLife 7:e32402.
https://doi.org/10.7554/eLife.32402