Medical Oncology

, 33:45 | Cite as

Potential of sulfasalazine as a therapeutic sensitizer for CD44 splice variant 9-positive urogenital cancer

  • Tatsuya TakayamaEmail author
  • Taro Kubo
  • Ai Morikawa
  • Tatsuo Morita
  • Osamu Nagano
  • Hideyuki Saya
Original Paper


Cancer stem-like cells (CSCs) with high expression of CD44 splice variant (CD44v) have an enhanced capacity for intracellular reduced glutathione synthesis and defense against reactive oxygen species, resulting in resistance to various therapeutic stresses. Sulfasalazine (SSZ), a drug used in the treatment of rheumatoid arthritis (RA), inhibits glutamate–cystine transport, and suppressed CD44v-dependent tumor growth and increased sensitivity to cytotoxic drugs in an in vivo study. Here, we present two cases of CD44v9-positive urogenital cancer with concomitant treatment with SSZ for RA. Patient 1 was a 62-year-old man who had received SSZ for RA beginning 2 months before the diagnosis of urinary bladder cancer. Although he had multiple metastases to the bladder, abdominal, left cervical and left axillary lymph nodes, and brain, complete response with multidisciplinary therapy was maintained for more than 2 years. Patient 2 was a 74-year-old man with castration-resistant prostate cancer who was diagnosed with RA during chemotherapy and a gradual increase in prostate-specific antigen (PSA) level. When SSZ was added, his PSA value (ng/mL) decreased from 12.93 to 5.58 in only 2 weeks and then quickly rebounded, whereas levels of neuron-specific enolase, a neuroendocrine differentiator and CSC marker, remained almost unchanged. We therefore speculate that SSZ treatment may represent a new adjuvant treatment option for patients with CD44v9-positive urogenital cancer.


CD44 CD44 splice variant Sulfasalazine Cancer stem-like cells Bladder cancer Prostate cancer Urogenital cancer xCT Glutamate–cystine transporter 



This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), The Japan Agency for Medical Research and Development.

Compliance with ethical standards

Conflict on interest

The authors state that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Tatsuya Takayama
    • 1
    Email author
  • Taro Kubo
    • 1
  • Ai Morikawa
    • 1
  • Tatsuo Morita
    • 1
  • Osamu Nagano
    • 2
  • Hideyuki Saya
    • 2
  1. 1.Department of UrologyJichi Medical UniversityTochigiJapan
  2. 2.Division of Gene Regulation, Institute for Advanced Medical ResearchKeio University School of MedicineShinjuku-KuJapan

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