Active Cytotoxic Agents Research Articles

A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study.

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9-11, oxadiazole, pyrazole and sulfinyl analogs 13-15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0μM and 91.8%, and of 79.8% at concentration of 1.0μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity.

Microvesicle-Mediated Delivery of Minicircle DNA Results in Effective Gene-Directed Enzyme Prodrug Cancer Therapy.

An emerging approach for cancer treatment employs the use of extracellular vesicles, specifically exosomes and microvesicles, as delivery vehicles. We previously demonstrated that microvesicles can functionally deliver plasmid DNA to cells and showed that plasmid size and sequence, in part, determine the delivery efficiency. In this study, delivery vehicles comprised of microvesicles loaded with engineered minicircle (MC) DNA that encodes prodrug converting enzymes developed as a cancer therapy in mammary carcinoma models. We demonstrated that MCs can be loaded into shed microvesicles with greater efficiency than their parental plasmid counterparts and that microvesicle-mediated MC delivery led to significantly higher and more prolonged transgene expression in recipient cells than microvesicles loaded with the parental plasmid. Microvesicles loaded with MCs encoding a thymidine kinase (TK)/nitroreductase (NTR) fusion protein produced prolonged TK-NTR expression in mammary carcinoma cells. In vivo delivery of TK-NTR and administration of prodrugs led to the effective killing of both targeted cells and surrounding tumor cells via TK-NTR-mediated conversion of codelivered prodrugs into active cytotoxic agents. In vivo evaluation of the bystander effect in mouse models demonstrated that for effective therapy, at least 1% of tumor cells need to be delivered with TK-NTR-encoding MCs. These results suggest that MC delivery via microvesicles can mediate gene transfer to an extent that enables effective prodrug conversion and tumor cell death such that it comprises a promising approach to cancer therapy.

Design, Synthesis, and In Vitro Activity of Pyrazine Compounds.

Despite the fact that there are several anticancer drugs available, cancer has evolved using different pathways inside the cell. The protein tyrosine phosphatases pathway is responsible for monitoring cell proliferation, diversity, migration, and metabolism. More specifically, the SHP2 protein, which is a member of the PTPs family, is closely related to cancer. In our efforts, with the aid of a structure-based drug design, we optimized the known inhibitor SHP099 by introducing 1-(methylsulfonyl)-4-prolylpiperazine as a linker. We designed and synthesized three pyrazine-based small molecules. We started with prolines as cyclic amines, confirming that our structures had the same interactions with those already existing in the literature, and, here, we report one new hydrogen bond. These studies concluded in the discovery of methyl (6-amino-5-(2,3-dichlorophenyl)pyrazin-2-yl)prolylprolinate hydrochloride as one of the final compounds which is an active and acceptable cytotoxic agent.

Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers.

Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Accordingly, new quinazoline-based derivatives having the structural features of VEGFR-2 inhibitors were designed and synthesized. Anti-proliferative activities were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Compounds 26b, 29a, 29b and 30 showed excellent anti-cancer activities against all cell lines. Moreover, compound 31 was the most active with IC 50 values of 3.97 ± 0.2, 4.83 ± 0.2 and 4.58 ± 0.3 µM, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities, compound 31 showed a high activity against VEGFR-2 with an IC50 value of 2.5 ± 0.04 µM, almost equal to that of sorafenib (IC50 = 2.4 ± 0.05 µM). Further studies revealed the ability of this promising quinazoline derivative 31 to induce apoptosis and arrest cell cycle growth at G2/M phase. In vivo antitumor activities of the synthesized compounds revealed that compounds 30 and 31 possessed significant tumor growth inhibition effect. Molecular docking studies were also performed and finally we can say that VEGFR-2 inhibition confers the reported cytotoxic activities.

Remedial effects of casticin as an antioxidant on cisplatin induced oxidative damage in rat liver

Cisplatin (CP) is an active cytotoxic agent, which has been verified to be effective in multiple cancer regimen. In this study, potential antioxidant effects of casticin (CAS) were assessed against CP generated oxidative stress in rat liver. “Twenty-four male Sprague Dawley rats were divided into four experimental groups. Group-1 (control group) received only normal saline”. Group-2 was intraperitoneally injected with CP (10 mg/kg). Group-3 was orally provided by CAS (50 mg/kg) along with CP (10 mg/kg) injection at first day. Group-4 group was orally administered with CAS (50 mg/kg) throughout the experiment. The rats of group-1 indicated “increase in serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), while a significant decrease in the activities of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD)” was noticed, which revealed that CP generated oxidative stress in rat liver. Moreover, administration of CP increased the hydrogen peroxide (H2O2) concentration and level of “thiobarbituric acid reactive substances (TBARS)”, while reducing the % DNA head and head length in liver cell nuclei. CP disturbs the lobular structure of the liver and increased the sinusoidal dilation in rat liver. However, co-treatment with CAS successfully mitigated the CP generated DNA disruption, biochemical and pathological changes in rat liver. These findings revealed that an effective antioxidant, CAS, alleviated the CP generated hepatotoxicity and oxidative stress in rats.

Self-Strengthened Oxidation-Responsive Bioactivating Prodrug Nanosystem with Sequential and Synergistically Facilitated Drug Release for Treatment of Breast Cancer.

Although environment-sensitive prodrug-based nanoparticles (NPs) have developed rapidly, lots of prodrug NPs still show poor selectivity and efficiency of parent drug bioactivation because of tumor heterogeneity. Herein, self-strengthened bioactivating prodrug-based NPs are fabricated via co-encapsulation of oxidation-responsive thioether-linked linoleic acid-paclitaxel conjugates (PTX-S-LA) and β-lapachone (LPC) into polymeric micelles (PMs). Following cellular uptake, PMs first release LPC to significantly elevate the reactive oxidative species (ROS) level through NAD(P)H: quinone oxidoreductase-1 (NQO1) catalysis. Then, NQO1-generated ROS in combination with endogenous high ROS levels in tumor cells could synergistically facilitate PTX-S-LA to release the active cytotoxic agent PTX. Such a novel prodrug nanosystem exhibits self-strengthened prodrug bioactivation, ultraselective release, and cytotoxicity between cancer and normal cells, prolonged circulation time, and enhanced tumor accumulation, leading to high antitumor efficiency and superior biosafety. Our findings pave the new way for the rational design of oxidation-responsive prodrug NPs for high-efficacy cancer chemotherapy.

The Investigation of the Antitumor Agent Toxicity and Capsaicin Effect on the Electron Transport Chain Enzymes, Catalase Activities and Lipid Peroxidation Levels in Lung, Heart and Brain Tissues of Rats.

Cisplatin is one of the most active cytotoxic agents in cancer treatment. To clarify the interaction with mitochondria, we hypothesize that the activities of mitochondrial electron transport chain (ETC) enzymes succinate dehydrogenase (SDH) and cytochrome c oxidase (COX), nucleotide levels, as well as levels of catalase (CAT) enzyme and membrane lipid peroxidation (LPO) can be affected by cisplatin. There was a significant decrease of both SDH and COX activities in the lung, heart, and brain tissues at the 1st day after cisplatin exposure, and the observed decreased levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in comparison with the control could be because of cisplatin-induced mitochondrial dysfunction. The investigations suggested that cisplatin inhibits SDH, COX, and ATP synthase. The higher LPO level in the studied tissues after 1 and 4 days post-exposure to cisplatin compared to control can be inferred to be a result of elevated electron leakage from the ETC, and reactive oxygen species (ROS) can lead to wide-ranging tissue damage such as membrane lipid damage. Consequently, it was observed that capsaicin may have a possible protective effect on ETC impairment caused by cisplatin. The activities of SDH and COX were higher in heart and brain exposed to cisplatin + capsaicin compared to cisplatin groups, while LPO levels were lower. The investigated results in the cisplatin + capsaicin groups suggested that the antioxidant capacity of capsaicin scavenges ROS and prevents membrane destruction.

Biological evaluation of water soluble arene Ru(II) enantiomers with amino-oxime ligands

New water soluble, enantiopure arene ruthenium compound SRuSN-(1R,4S)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (Bn = benzyl, 1a′) has been synthesized. The novel compound along with that previously described RRuRN-(1S,4R)-[(η6-p-cymene)Ru{ĸNH(Bn),ĸNOH}Cl]Cl (1a) was evaluated by polarimetry, ultra-violet and circular dichroism spectroscopy. The structure of novel ruthenium derivative 1a′ was determined by single crystal X-ray crystallography. Both enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3, lung A-549, pancreas MIA PaCa-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. Both enantiomers are active and versatile cytotoxic agents, showing IC50 values from 2 to 12 times lower than those found for cisplatin in the different cell lines evaluated. The mechanism of cell death induced by the metal compounds was analyzed in A-549 and Jurkat cell lines. Derivatives 1a and 1a′ induced apoptotic cell death of A-549 cells while dose-dependent cell death mechanisms have been found in the Jurkat cell line. Compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, revealing moderate binding affinity of 1a and 1a′ towards duplex DNA. Finally, the efficacy of 1a in a preliminary in vivo assay of PC-3 xenografts in nude mice has been evaluated, resulting in a promising inhibition of tumor growth by 45%. Analysis of tumor tissue also showed a significant decrease of levels of crucial molecules in the invasive phenotype of PC-3 cells.

MA 16.04 Phase II Trial of S-1 Treatment as Palliative-Intent Chemotherapy for Previously Treated Advanced Thymic Carcinoma

Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival with palliative-intent chemotherapy. Sunitinib and everolimus monotherapies have been proposed as active molecular-targeted approaches based on phase II (Ph II) trials, and S-1, an oral fluoropyrimidine, has been described in the NCCN guideline as an active cytotoxic agent for refractory TC based on a case series. Therefore, we conducted a Ph II trial to study the result of S-1 treatment in patients with refractory TC.

Traitement de première ligne et de maintenance dans les CBNPC avancés en l’absence d’addiction oncogénique

Since 25 years, first-line treatment of metastatic NSCLC without oncogenic addiction has been based on chemotherapy regimen combining a platinum salt and an active cytotoxic agent, mainly third generation agent, with similar results for the different available schedules which were primarily selected on toxicity profile. Improvement of chemotherapy results derived from taking into account histological subtype, with the development of pemetrexed and maintenance strategies mainly based on pemetrexed continuation as single agent and the addition of bevacizumab to chemotherapy for non-squamous carcinoma. The development of immunotherapy and for the most part checkpoints inhibitors leads to a new paradigm, targeting not anymore directly the cancer cells but the T cells responsible for the destruction of tumour cells. The anti-PD-1 pembrolizumab is thus the standard of care in first-line setting of NSCLC with PD-L1 expression in more than 50% of tumour cells, replacing for the first time cytotoxic chemotherapy and resulting in long-lasting responses. Development of treatment combinations around checkpoints inhibitors might soon lead to further changes in the treatment algorithm of advanced NSCLC and to chemotherapy step back.

Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin via regulating microRNA expression

BackgroundEmerging evidence suggests that curcumin can overcome drug resistance to classical chemotherapies, but poor bioavailability and low absorption have limited its clinical use and the mechanisms remain unclear. Also, Adriamycin (Adr) is one of the most active cytotoxic agents in breast cancer; however, the high resistant rate of Adr leads to a poor prognosis. MethodsWe utilized encapsulation in liposomes as a strategy to improve the bioavailability of curcumin and demonstrated that liposomal curcumin altered chemosensitivity of Adr-resistant MCF-7 human breast cancer (MCF-7/Adr) by MTT assay. The miRNA and mRNA expression profiles of MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr cells were analyzed by microarray and further confirmed by real-time PCR. We focused on differentially expressed miR-29b-1-5p to explore the involvement of miR-29b-1-5p in the resistance of Adr. Candidate genes of dysregulated miRNAs were identified by prediction algorithms based on gene expression profiles. Networks of KEGG pathways were organized by the selected dysregulated miRNAs. Moreover, protein–protein interaction (PPI) was utilized to map protein interaction networks of curcumin regulated proteins. ResultsWe first demonstrated liposomal curcumin could rescue part of Adriamycin resistance in breast cancer and further identified 67 differentially expressed microRNAs among MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr. The results showed that lower expressed miR-29b-1-5p decreased the IC50 of MCF-7/Adr cells and higher expressed miR-29b-1-5p, weaken the effects of liposomal curcumin to Adr-resistance. Besides, we found that 20 target genes (mRNAs) of each dysregulated miRNA were not only predicted by prediction algorithms, but also differentially expressed in the microarray. The results showed that MAPK, mTOR, PI3K-Akt, AMPK, TNF, Ras signaling pathways and several target genes such as PPARG, RRM2, SRSF1and EPAS1, may associate with drug resistance of breast cancer cells to Adr. ConclusionsWe determined that an altered miRNA expression pattern is involved in acquiring resistance to Adr, and that liposomal curcumin could change the resistance to Adr through miRNA signaling pathways in breast cancer MCF-7 cells.

Synthesis and Biological Evaluation of Chalcones Possessing Ring Activating Groups as Potent of Anticancer Agents

Some novel anticancer agents based on chalcone scaffold were synthesized with potential therapeutic application for many types of cancer. Hydroxy and methoxy substitution on aryl ring of chalcone, depending upon positions in aryl ring influence anticancer and other activities. These chalcone molecules were evaluated for their invitro cytotoxic activity against five cancer cell lines including human chronic myelogenus-leukemia K-562, human breast adenocarcinoma MCF-7, human prostate carcinoma DU-145, human lung adenocarcinoma A-549 and normal VERO cell line. Most of the compounds being active cytotoxic agents and were shown to be non-toxic to normal cells. The synthesized compounds were characterized by means of their FT-IR, MASS and 1HNMR spectral study.

Synthesis and Biological Evaluation of Chalcones Possessing Ring Activating Groups as Potent of Anticancer Agents

Some novel anticancer agents based on chalcone scaffold were synthesized with potential therapeutic application for many types of cancer. Hydroxy and methoxy substitution on aryl ring of chalcone, depending upon positions in aryl ring influence anticancer and other activities. These chalcone molecules were evaluated for their invitro cytotoxic activity against five cancer cell lines including human chronic myelogenus-leukemia K-562, human breast adenocarcinoma MCF-7, human prostate carcinoma DU-145, human lung adenocarcinoma A-549 and normal VERO cell line. Most of the compounds being active cytotoxic agents and were shown to be non-toxic to normal cells. The synthesized compounds were characterized by means of their FT-IR, MASS and 1HNMR spectral study.

Utilization of systemic therapy options in the routine treatment of metastatic colorectal cancer.

738 Background: In the treatment of metastatic colorectal cancer (mCRC), exposure to all three active cytotoxic agents; 5-fluorouracil/capecitabine (FP), irinotecan (Ir) and oxaliplatin (Ox), and the biologic agents, bevacizumab (Bev) and cetuximab and panitumumab (EGFR-I) improves outcomes. The current uptake of systemic agents for mCRC in a community setting in Australia is poorly described. Methods: The ACCORD database was interrogated to determine demographics, treatments and outcomes for all patients diagnosed with mCRC between 1/01/2011 and 1/01/2015 at 6 Melbourne centres (3 public and 3 private). Results: 865 patients were identified: median age was 68 years. 68% were ECOG 0-1, 60% had de novo metastatic disease. RAS status was known in 59%, of whom 48% were RAS wild-type (WT). At the time of analysis 69% of all patients had received systemic treatment with 51% receiving treatment second line and beyond; 65% RAS WT, 57% RASm, 16% RAS-Unk. See Table. Metastasectomy was performed in 29% of patients of whom 38% remain disease-free. With a median follow-up of 31.3 months 46% of patients remain alive. The median overall survival was 25 months for all patients(unresected;17.6 months, resected: not reached). Conclusions: A high proportion of patients receiving routine clinical care in the community setting do not receive any systemic therapy and few patients receive all available active agents. Despite this, the overall survival of patients with mCRC in this community-based cohort was 25 months and in-line with clinical trial data. [Table: see text]

Nab-paclitaxel after docetaxel hypersensitivity reaction: case report and literature review

Taxanes, including paclitaxel and docetaxel, are one of the most active cytotoxic agents in breast cancer treatment including Her-2 positive subtype characterized by aggressive clinical and pathological features since the early stage. However, their use is sometimes limited by the occurrence of hypersensivity reactions (HSRs) characterized by erythematous rashes, bronchospasm, respiratory distress, hypotension, and pulmonary edema. Cross-reactions between paclitaxel and docetaxel are described in literature with a rate ranging from 49% to 90%. Abraxane (nab-paclitaxel), an albumin-bound form of paclitaxel, has a different toxicity profile from solvent-based paclitaxel and a lower rate of HSRs. Interestingly, several authors have recently reported cases of patients who developed HSRs to taxanes, principally paclitaxel, and were then safety treated with Abraxane, suggesting the absence of cross-reactivity between these drugs. Based on these considerations, we report our clinical experience and perform a literature review on this topic with the aim to investigate the cross-reactivity between nab-paclitaxel and other taxanes, in particular with docetaxel. (www.actabiomedica.it)

Bu-Zhong-Yi-Qi Decoction, the Water Extract of Chinese Traditional Herbal Medicine, Enhances Cisplatin Cytotoxicity in A549/DDP Cells through Induction of Apoptosis and Autophagy.

Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects. Cotreatment with BZYQD and cisplatin induced intrinsic apoptotic pathways which were measured by condensed nuclear chromatin, Annexin V/PI apoptosis assay, and apoptosis related proteins expression. In addition, cotreatment with BZYQD and cisplatin also activated autophagy, as indicated by an increase in LC3 puncta, classical autophagosomes and/or autolysosomes, and an accumulation of LC3-II and ATG7 protein. Finally, cotreatment with BZYQD and cisplatin resulted in the generation of ROS and scavenging ROS by NAC almost completely suppressing cell death. These results suggest that cotreatment with BZYQD and cisplatin might reverse cisplatin resistance by inducing ROS accumulation, which activates apoptosis and autophagy by oxidative stress. The combination of BZYQD and cisplatin may represent a novel approach in treatment for NSCLC and thus offer a new target for chemotherapy.

Age-related systemic treatment and survival of patients with metachronous metastases from colorectal cancer

Background: Although the spectrum of systemic treatment for metastatic colorectal cancer (mCRC) has widened, there is a paucity of evidence for the feasibility and optimal use of these systemic agents in elderly patients. The present study provides real world data on the age-related systemic treatment and survival of CRC patients with non-resectable metachronous metastases.Methods: All consecutive patients with non-resectable metastases from primary resected CRC were extracted from the Eindhoven area of the Netherlands Cancer Registry (NCR). Patients receiving palliative systemic therapy were enrolled (n = 385). Systemic treatment and survival were analyzed according to age at diagnosis of metastases.Results: Patients aged ≥75 years more often received first-line single-agent chemotherapy than their younger counterparts (63% vs. 32%, p < .0001). First-line single-agent chemotherapy was often prescribed without additional targeted therapy (78%). Advanced age (≥75 years) was associated with a lower probability of receiving all active cytotoxic agents compared to patients aged <60 years at time of diagnosis of metastases (odds ratio (OR) 0.2, 95% CI 0.10–0.77). In a multivariable Cox regression analysis with adjustment for age and other relevant prognostic factors, the total number of received systemic agents was the only predictor of death (hazard ratio (HR) 0.7, 95% CI 0.61–0.81).Conclusion: The beneficial effect of treatment with all active systemic agents on survival (simultaneously or sequentially prescribed) should be taken into account when considering systemic therapy in patients with mCRC. In light of our results, future studies are warranted to clarify the role of potential targeted therapy in elderly mCRC patients, who are often not candidates for combination chemotherapy and treatment with all active cytotoxic agents.

Influence of cytotoxic butyltin complexes with 2-sulfobenzoic acid on the thermotropic phase behavior of lipid model membranes

In the previous study, we showed that butyltin complexes with 2-sulfobenzoic acid (commonly referred to as BTsbz) exhibit a very wide biological activity. The BTsbz in vitro are very active cytotoxic agents against tumor cells—more effective than cisplatin and carboplatin (traditional anticancer drugs). These complexes are antibacterial agents against gram-positive and gram-negative bacteria, as well. The aim of the present study was to investigate the influence of BTsbz on the thermotropic phase behavior of dipalmitoylphosphatidylcholine (DPPC) model membranes. The effect of this compound on the multilamellar liposomes was studied mainly by the means of differential scanning calorimetry and additionally by the steady-state fluorimetry and infrared spectroscopy. All investigated butyltin complexes with 2-sulfobenzoic acid change the thermotropic properties of lipid model membranes: The temperature of the main phase transition of DPPC is slightly decreased, and the transition’s cooperativity of the peak is very much reduced. With increasing concentration, all investigated compounds abolished the pretransition. The results suggest that BTsbz are very active in the hydrophilic area of DPPC bilayer and at the same time have an effect on membrane fluidity.

Oleanolic Acid A-lactams Inhibit the Growth of HeLa, KB, MCF-7 and Hep-G2 Cancer Cell Lines at Micromolar Concentrations.

Oleanolic acid ketones, oximes, lactams and nitriles were obtained. Complete spectral characterizations (IR, (1)H NMR, (13)C NMR, DEPT and MS) of the synthesized compounds are presented. The derivatives had oxo, hydroxyimino, lactam or nitrile functions at the C-3 position, an esterified or unmodified carboxyl group at the C- 17 location and, in some cases, an additional oxo function at the C-11 position. The new compounds were tested for cytotoxic activity on the HeLa, KB, MCF-7 and Hep-G2 cancer cell lines with the application of MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. Among the tested compounds, some oximes and all lactams proved to be the most active cytotoxic agents. These triterpenes significantly inhibited the growth of the HeLa, KB, MCF-7 and Hep-G2 cancer cell lines at micromolar concentrations.

Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma.

BackgroundThymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis.MethodsWe assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort.ResultsA total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4–67.4) and the disease control rate was 85.7 % (60.0–96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6–12.2 months), and median overall survival was 30.0 months (range, 6.2–41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed.ConclusionsS-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2159-7) contains supplementary material, which is available to authorized users.