ArticleCancer science2017
Phase I study of salazosulfapyridine in combination with cisplatin and pemetrexed for advanced non-small-cell lung cancer.
Article in Cancer science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
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- CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.Stem cells (Dayton, Ohio) · 2025Review
- CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb.FEBS open bio · 2025Article
- Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairsJournal of pharmaceutical analysis · 2025Article
- Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review).Oncology letters · 2024Review
- Iron metabolism: backfire of cancer cell stemness and therapeutic modalities.Cancer cell international · 2024Review
- Article
- Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells.The Journal of veterinary medical science · 2023Article
- RNA splicing alterations in lung cancer pathogenesis and therapy.Cancer pathogenesis and therapy · 2023Review
- Mechanism of Cell Death by Combined Treatment with an xCT Inhibitor and Paclitaxel: An Alternative Therapeutic Strategy for Patients with Ovarian Clear Cell Carcinoma.International journal of molecular sciences · 2023Article
- Clinical relevance of stem cells in lung cancer.World journal of stem cells · 2023Review
- Inhibition of lung adenocarcinoma by combinations of sulfasalazine (SAS) and disulfiram-copper (DSF-Cu) in cell line models and mice.Carcinogenesis · 2023Article
- Article
- Therapy-resistant nature of cancer stem cells in view of iron metabolism.Inflammation and regeneration · 2022Review
- Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia.Leukemia · 2022Article
- Establishment of a New Canine Inflammatory Mammary Carcinoma Cell Line and Analysis of its Cystine-glutamate Transporter Subunit Expression.Journal of veterinary research · 2022Article
- Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy.World journal of stem cells · 2022Review
- Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review.Dermatology and therapy · 2022Review
- Pharmacogenomics Testing in Phase I Oncology Clinical Trials: Constructive Criticism Is Warranted.Cancers · 2022Review
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spliced variant isoforms of CD44 (CD44v) are a marker of cancer stem cells in solid tumors. They stabilize the xCT subunit of the transporter system xc(-) and thereby promote synthesis of the antioxidant glutathione. Salazosulfapyridine (SASP) is an inhibitor of xCT and suppresses the proliferation of CD44v-positive cancer cells. Chemotherapy-naïve patients with advanced non-squamous non-small-cell lung cancer were enrolled in a dose-escalation study (standard 3 + 3 design) of SASP in combination with cisplatin and pemetrexed. The primary end-point was the percentage of patients who experience dose-limiting toxicity. Fifteen patients were enrolled in the study. Dose-limiting toxicity was observed in one of six patients at a SASP dose of 1.5 g/day (elevation of aspartate and alanine aminotransferase levels, each of grade 3), two of five patients at 3 g/day (hypotension or pneumonitis, each of grade 3), and two of three patients at 4.5 g/day (anorexia of grade 3). The maximum tolerated dose was thus 3 g/day, and the recommended dose was 1.5 g/day. The overall response rate was 26.7% and median progression-free survival was 11.7 months, much longer than that for cisplatin-pemetrexed alone in previous studies. Exposure to SASP varied markedly among individuals according to ABCG2 and NAT2 genotypes. The serum concentration of free CD44v protein was increased after the first cycle of treatment, possibly reflecting death of cancer stem cells. Salazosulfapyridine was thus given safely in combination with cisplatin-pemetrexed, with the addition of SASP tending to prolong progression-free survival. This trial is registered in the UMIN Clinical Trials Registry as UMIN000017854.
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