Primary cilia are antenna‑like organelles on almost all human cells that sense and transduce extracellular cues into cellular response. Primary cilia have been reported to be implicated in drug resistance in several cancer types, but their roles in cellular response to epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitors (TKIs) in non‑small cell lung cancer (NSCLC) are still not fully understood. In the present study, it was reported that primary cilia are more prevalent in EGFR‑TKI‑insensitive A549 and H23 cells compared with the drug‑sensitive HCC827 and PC9 cells by immunofluorescence staining assay. Importantly, treatment with EGFR‑TKIs (gefitinib and dacomitinib) results in a dose‑dependent increase in cilia number and length in A549 and H23 cells, an effect not observed in HCC827 and PC9 cells. Upon administration of gefitinib, A549 cells predominantly arrest in the G1 phase detected by flow cytometric analysis, with a minority undergoing cell death and the majority entering senescence. Inhibition of ciliogenesis through the knockdown of IFT88 or ARL13B by targeted small interfering RNAs markedly enhances the sensitivity of A549 cells to EGFR‑TKIs by promoting a shift from senescence to cell death. Furthermore, it was demonstrated by immunoblotting and immunofluorescence colocalization analysis that both the expression and ciliary localization of adenylate cyclase 3 (AC3) are significantly upregulated following EGFR‑TKIs treatment, and the reduction of AC3 expression effectively mitigates cellular drug resistance in A549 cells. These findings highlight a critical role for the cilia‑AC3 axis in modulating cellular response to EGFR‑TKIs, suggesting it as a potential therapeutic target for the treatment of NSCLC.

Alternative splicing (AS) is one of the principal mechanisms of post‑transcriptional regulation that confers transcriptomic plasticity and proteomic diversity in cancer, thereby enabling tumor adaptation to therapeutic pressure. However, two obstacles impede the translation of these findings into clinical benefit: The absence of systematic functional annotation of the numerous splice variants associated with drug resistance and the paucity of biomarkers capable of distinguishing from acquired splice‑mediated resistance. In the present review, the current mechanistic understanding of AS‑driven drug resistance was briefly synthesized, and it was evaluated how existing strategies address these challenges. It was also described how knowledge of dysregulated splicing networks, due to mutations in cis‑regulatory elements such as ESS, overexpression of trans‑acting factors such as , as well as mechanisms such as alternative trans‑splicing, in which the spliceosome interacts with splice sites on two distinct RNA molecules and which can be driven by complementary sequences or other trans‑acting factors, could be used to more accurately identify tumors dependent on aberrant splicing for survival. In addition, it was outlined how targeting aberrant splice variants to overcome therapeutic resistance can be achieved, such as through spliceosome inhibition (for example, H3B‑8800) or antisense oligonucleotides directed to a specific exon or splice junction (for example, targeting exon 2 of , which is implicated in cis‑regulated AS isoforms, or alternatively spliced isoforms of , and ). However, therapeutic strategies to target adaptive resistance mechanisms such as AS remain limited, as intratumoral heterogeneity may facilitate the emergence of resistant subpopulations, and as most spliceosome inhibitors are not spliceosome‑specific, they exhibit off‑target effects. Importantly, it was also discussed how pan‑cancer splicing databases and single‑cell isoform expression profiling can be integrated with deep‑learning models, thereby informing the design of therapeutic strategies to overcome splicing‑mediated adaptive drug resistance. Notably, such integration will enable the rational design of isoform‑specific combination regimens to dismantle drug‑resistance circuits. It is anticipated that the present review will assist the scientific community, including both basic and translational researchers, in translating these findings into interventions that mitigate therapeutic failure in recalcitrant cancers.

Subsequently to the publication of the above paper, a concerned reader has drawn to the Editor's attention that, for the western blot data shown in Fig. 2A and B on p. 71, certain of the protein bands looked strikingly similar to others, where the results of differently performed experiments were intended to have been represented (considering both the forward orientations of the bands in question, and occasionally, bands positioned in the reverse orientation). The Editorial Office has investigated this matter independently, and reached the same concluson as the reader that certain of the data appeared to have been duplicated within Fig. 2A and B. Given that this issue has come to light, the Editor of has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 34: 67‑76, 2015; DOI: 10.3892/or.2015.3999].

Cancer is increasingly recognized not as a fixed genetic condition but as a dynamic and plastic disease state driven by reversible epigenetic, transcriptional and microenvironmental cues. This evolving understanding supports a therapeutic paradigm shift: from eradicating malignant cells to reprogramming them toward quiescence, differentiation or functional normalization. This review explores diverse strategies for redirecting cancer cell fate, including differentiation therapy, epigenetic remodeling, lineage reprogramming, senescence induction and tumor microenvironment resetting. These approaches exploit intrinsic cellular plasticity and contextual adaptability, offering novel avenues to contain malignancy and overcome resistance. By reframing cancer as a potentially reversible phenotype, this therapeutic strategy demands redefinition of clinical endpoints, incorporation of dynamic biomarkers, and development of integrative treatment frameworks. Ultimately, reprogramming‑based oncology holds the promise of transforming aggressive malignancies into manageable conditions while minimizing the collateral damage associated with conventional cytotoxic therapies.

Gemcitabine (GEM) is the first‑line chemotherapy drug for pancreatic cancer, but its efficacy is often limited by inherent drug resistance. Saikosaponin D (SSD), a bioactive triterpenoid saponin derived from the root, exhibits anti‑inflammatory and antitumor properties; however, to the best of our knowledge, its role in pancreatic cancer and GEM sensitization remains unclear. The present study investigated the effects of SSD on the proliferation, apoptosis and autophagy of pancreatic cancer cells, and evaluated whether SSD can overcome GEM resistance to enhance its antitumor effects. Using MIA PaCa‑2 and AsPC‑1 cells, the sensitivity to SSD and GEM was assessed using Cell Counting Kit‑8 assays, H&E staining and colony formation assays. Optimal sub‑lethal concentrations of GEM (0.25 µmol/l), SSD (4 µmol/l) and their combination (0.25 µmol/l GEM + 4 µmol/l SSD) were identified. Apoptosis was evaluated through Hoechst 33258 staining and TUNEL assays, while autophagy was measured using the monodasylcadaverine method. Western blotting and immunocytochemical staining were used to analyze the expression levels of proteins related to apoptosis, AKT/mTOR signaling and autophagy. The results demonstrated that the SSD + GEM combination significantly inhibited pancreatic cancer cell proliferation in both MIA PaCa‑2 and AsPC‑1 cell lines, with proliferation being suppressed by nearly half. Similarly, the combination treatment induced apoptosis and enhanced autophagosome formation, suggesting potential synergistic effects when compared with GEM monotherapy. In conclusion, SSD synergistically enhanced the antitumor effects of GEM by inhibiting pancreatic cancer cell proliferation, and inducing apoptosis and autophagy. SSD may overcome GEM resistance by sensitizing cells through AKT/mTOR pathway inhibition.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrous stroma, within which a subset of fibroblasts function as cancer‑associated fibroblasts (CAFs) and contribute to tumor progression. Some of these fibroblasts undergo senescence and promote malignancy through the senescence‑associated secretory phenotype (SASP). The present study investigated SASP factor expression in senescent fibroblasts within the PDAC microenvironment and evaluated their impact on tumor progression. The expression levels of the senescence marker p16 and the SASP factor interleukin‑6 (IL‑6) were assessed using fluorescence immunostaining in resected specimens from 90 patients with PDAC who underwent pancreaticoduodenectomy. Senescence was induced in primary human pancreatic fibroblasts via X‑ray irradiation , followed by evaluation of SASP factor expression. These senescent fibroblasts were then co‑cultured with human pancreatic cancer Panc‑1 cells to assess their effects on cancer cell invasion, migration and proliferation. Immunostaining demonstrated the presence of p16‑ and IL‑6‑expressing fibroblasts in the PDAC stroma of patient samples. A positive correlation was observed between p16 and IL‑6 expression levels in fibroblasts. Notably, increased expression levels of IL‑6‑positive fibroblasts were associated with reduced postoperative survival. Multivariate analysis identified high IL‑6 expression and lymph node metastasis as independent prognostic indicators of poor outcome. In co‑culture experiments, senescent fibroblasts enhanced Panc‑1 cell invasion, migration and proliferation. These findings suggested that senescent fibroblasts within the PDAC stroma, with high SASP factor expression, contribute to tumor aggressiveness and are associated with poor prognosis. The present study demonstrated that IL‑6‑expressing senescent fibroblasts are potential prognostic markers and therapeutic targets in PDAC, therefore the targeted elimination of senescent cells may represent a promising therapeutic strategy.

Following the publication of the above article, a concerned reader drew to the Editor's attention that one set of the tumor data comparing between the 'CD44' experiments in Fig. 4A and the 'CON' experiments in Fig. 4B on p. 428 had apparently been duplicated; moreover, several of the images of various of the mice shown in this figure looked more similar in appearance than might have been expected. Furthermore, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the data panel showing the results of the migratory assay experiment relating to the 'KD' group in Fig. 2B on p. 926 contained an internally duplicated area that would have been difficult to attribute to coincidence. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. Therefore, the Editor of has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 923‑931, 2016; DOI: 10.3892/or.2015.4414].

Treatment options for triple‑negative breast cancer (TNBC) are limited because they typically harbor a high cancer stem‑like population and exhibit a relatively aggressive metastatic phenotype. Heat shock protein 90 (HSP90), a molecular chaperone that regulates diverse oncogenic client proteins, has emerged as a compelling therapeutic target owing to its involvement in key tumor‑promoting processes, such as uncontrolled proliferation, angiogenesis and metastasis. Owing to the undesirable induction of a compensatory heat shock response (HSR) and systemic toxicity, classical N‑terminal inhibitors of HSP90 have failed in clinical trials. The impact of a rationally designed novel inhibitor of the HSP90 C‑terminus in TNBC cells was investigated. NCT‑58 eliminates rapidly proliferating tumor cells accompanied by simultaneous degradation of AKT, MEK and STAT3, and effectively eradicates the cancer stem‑like population (breast cancer stem cells) in both human MDA‑MB‑231 and murine 4T1 cells. The latter phenomenon is accompanied by reductions in the activity of ALDH1 and the CD44/CD24 stem‑like population, as well as impairment of mammosphere formation. Furthermore, NCT‑58 markedly impairs cell migration, coinciding with the collapse of HSP90 client cytoskeletal proteins, including vimentin and F‑actin, in MDA‑MB‑231 cells . A synergistic effect was observed when NCT‑58 was combined with paclitaxel or doxorubicin in MDA‑MB‑231 cells. Collectively, these findings indicated that targeting the C‑terminal domain of HSP90 with NCT‑58 is a promising therapeutic strategy for the treatment of molecularly heterogeneous TNBC.

Glioblastoma (GBM), the most common type of primary malignant brain tumor, is characterized by aggressive cancer cells that contribute to infiltrative growth, thus resulting in therapeutic challenges and a poor prognosis. To explore the molecular mechanisms underlying cell motility and to identify therapeutic targets that may intervene in tumor invasion, public databases were used to investigate the S100B expression profile and the prognosis of patients with tumors. The effects of S100B on a GBM cell line were assessed through lentiviral transduction, as well as cell viability, colony formation, 5‑ethynyl‑2'‑deoxyuridine‑based cell proliferation, cross‑scratch, and Transwell migration and invasion assays. In addition, a tumor xenograft model was constructed to analyze tumor growth . Reverse transcription-quantitative PCR, western blotting and immunofluorescence staining were utilized to explore the molecular biological mechanisms of the TGF‑β2‑induced epithelial‑mesenchymal transition (EMT) in the S100B‑downregulated group. The findings demonstrated that S100B was significantly upregulated in GBM samples and was strongly associated with patient prognosis. and experiments confirmed that downregulation of S100B effectively suppressed the proliferation and tumorigenicity, as well as decreased the invasive and migratory capabilities of LN229 glioblastoma cells. Further investigation revealed that the inhibition of S100B resulted in downregulation of TGF‑β2 expression and reversal of the EMT process. Notably, recombinant TGF‑β2 restored the cell motility and EMT capacities attenuated by the downregulation of S100B. In conclusion, the present study revealed that S100B may induce the invasion and migration of GBM cells through TGF‑β2‑induced EMT, providing novel insights and potential therapeutic targets for GBM.

Following the publication of this paper, and the publication of an Expression of Concern statement (doi.org/10.3892/or.2025.8979), the authors have replied concerning an issue that was drawn to our attention by an interested reader; namely, that the immunohistochemical images shown in Figs. 1E and 5E appeared to show an overlapping section, even though Figs. 1 and 5 were intended to show the results of SHP2 and Ras expression experiments, respectively. The authors were able to check their data, and realized that Fig. 5 had inadvertently been assembled incorrectly. The revised version of Fig. 5, now showing the correct data for Fig. 5E, is shown below. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Oncology  Reports 39: 611‑618, 2018; DOI: 10.3892/or.2017.6109.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the 'Mock' and 'mimic‑18a NC' data panels shown in Fig. 5A for the SiHa flow cytometric (FCM) experiments were remarkably similar in appearance, even though their gated percentages were reported differently. Upon performing an independent analysis of the data in the Editorial Office, it came to light that various of the data quadrants shown in this figure were strikingly similar to FCM data in articles written by different authors at different research institutes that were published subsequently in other journals, one of which has been retracted on account of data re‑use issues; in addition, data were apparently duplicated in Fig. 10A, where the same data had been used to show the results of differently performed experiments. Given the nature of the contentious issues repported above, the Editor of has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 33: 2853‑2862, 2015; DOI: 10.3892/or.2015.3929].

Subsequently to the publication of the above paper, the authors have drawn to the attention of the Editorial Office that they made an error in assembling the western blot data in Fig. 3C on p. 6; namely, that the western blot data correctly selected for the P53 protein with the SW620 cell line (right-hand gels) had inadvertently also been included for the γ-H2A.X protein blots with the HCT116 cell line (left-hand gels). Upon analysing this figure further in the Editorial Office, we notified the authors of possibly overlapping α-tubulin control blots for the SW62 cell line in the same figure part, and the authors realized that one of these blots had similarly been chosen incorrectly. The revised version of Fig. 3, now showing the correct γ-H2A.X data for the HCT116 cell line and the correct α-tubulin protein blots for the SW620 cell line, is shown on the next page. The authors wish to emphasize that the corrections made to this figure do not affect the overall conclusions reported in the paper, and they are grateful to the Editor of for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum, and also apologize to the readership for any inconvenience caused. [Oncology Reports 51: 70, 2024; DOI: 10.3892/or.2024.8729].

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Fig. 4B were remarkably similar to the data shown in Fig. 2B for the CAL‑27 experiments, albeit the panels in the latter figure were shown rotated through 90/180° relative to the former figure. Moreover, upon performing an independent analysis of the data in the Editorial Office, it came to light that some of the flow cytometric data in Fig. 2C were strikingly similar to data that had appeared previously in an article in the journal that was written by different authors at different research institutes. Given that the contentious data in the above paper had apparently already been published in an unrelated article prior to its submission to , the Editor has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 34: 2961‑2968, 2015; DOI: 10.3892/or.2015.4323].

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the blots showing β‑actin mRNA expression in Fig. 1 on p. 1341 appeared to be similar to the β‑actin mRNA blots shown in Fig. 3 on p. 1342, albeit with some horizontal and vertical resizing. The authors were contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 19: 1339‑1345, 2008; DOI: 10.3892/or.19.5.1339].

Esophageal cancer is a highly prevalent malignancy worldwide. Although immunotherapy, particularly programmed cell death‑1/programmed cell death ligand 1 (PD‑1/PD‑L1) inhibitors, has notably improved patient outcomes, the overall response rate remains limited. This limited efficacy is largely attributed to complex immunosuppressive networks within the tumor microenvironment (TME). The present review systematically dissects the multifaceted regulatory mechanisms of the PD‑1/PD‑L1 signaling axis in the TME of esophageal squamous cell carcinoma (ESCC), and its impact on immunotherapeutic efficacy. Emerging evidence indicates that multiple immunosuppressive mechanisms within the TME shape the response to immune checkpoint inhibitors: Regulatory T cells enhance immunosuppression via the TGF‑β‑PD‑1/PD‑L1 axis; IL‑6/STAT3 signaling upregulates PD‑L1 expression and mitochondrial remodeling and amino acid network regulation exacerbate T cell exhaustion. Meanwhile, tertiary lymphoid structure (TLS) maturation is positively associated with clinical prognosis by promoting tissue‑resident memory T cell activation and enhancing antitumor immunity. By contrast, the predictive value of tumor mutational burden (TMB) is constrained by TME heterogeneity. Emerging strategies highlight the predictive potential of TLS maturity and TMB, although the predictive relevance of TMB in ESCC remains inconsistent. Combination approaches show promise in reversing T/natural killer cell exhaustion and remodeling immunosuppressive TMEs. Future research should combine multi‑omics data with clinical information to develop personalized immunotherapy models for ESCC.

Melanoma, a highly malignant form of skin cancer, poses significant challenges in oncology due to its aggressive nature and resistance to conventional therapies. Epigenetic modifications, especially acetylation, have emerged as critical regulators of gene expression that influence the pathogenesis and progression of melanoma. Acetylation is a novel post‑translational modification that involves the addition of an acetyl group to lysine residues both in histone and in non‑histone proteins. In the context of melanoma, acetylation has been shown to occupy a pivotal role in regulating cellular proliferation, autophagy, apoptosis and metastasis, as well as drug resistance. The identification of acetylation‑associated biomarkers and therapeutic targets in melanoma is currently an active area of research. The present review aims to elucidate the roles of acetylation modifications in melanoma, and to explore the potential of targeting these modifications for novel therapeutic interventions, with a unique perspective on the acetylation networks mediating therapy resistance.

Ferroptosis is a type of programmed cell death characterized by accumulation of free iron, reactive oxygen species generation and lipid peroxidation and is distinct from other types of regulated cell deaths such as apoptosis, necrosis and autophagy. Ferroptosis is distinct from other programmed cell deaths for its iron dependence and its significant role in tumor suppression. Therefore, harnessing ferroptosis may offer promising avenues for cancer therapy. In the present review, the different pathways that lead to ferroptosis, the genes and transcription factors involved in both iron and lipid metabolism, as well as the impact of small‑molecule alterations on the regulation of ferroptotic cell death, were discussed. Furthermore, the emergence of combination therapies with ferroptosis‑inducing molecules that overcome resistance to conventional chemotherapy, particularly in solid tumors, were highlighted.

Leukemia is a group of hematologic malignancies characterized by the uncontrolled proliferation of abnormal white blood cells, posing significant challenges for diagnosis and treatment because of its complex etiology. Both genetic and environmental factors contribute to leukemogenesis, with recent research highlighting the critical role of epigenetic modifications, particularly histone acetylation and deacetylation, in regulating gene expression and disease progression. Dysregulation of histone deacetylases (HDACs) is frequently observed in leukemia and is correlated with poor prognosis and resistance to conventional therapies. This observation has led to the development of epigenetic drugs for leukemia treatment. The emergence of HDAC inhibitors (HDACis) as targeted therapeutics offers promising avenues for more selective and effective leukemia treatments. The present review covers basic aspects of histone modification and its role in leukemogenesis and evaluates the potential of peptide‑based HDACis as novel drugs for leukemia therapy.

Non‑small cell lung cancer (NSCLC), accounting for >85% of LC cases, remains a therapeutic challenge due to its low 5‑year survival rate, tumor heterogeneity and drug resistance. The SRY‑related high‑mobility group‑box (SOX) family comprises transcription factors involved in the initiation and progression of NSCLC. These factors regulate epithelial‑mesenchymal transition and angiogenesis, interact with epidermal growth factor receptor/KRAS pathways to influence tumor invasion and promote chemotherapy resistance by sustaining tumor stemness. The present review aimed to summarize the expression patterns, molecular mechanisms and clinical relevance of SOX family members (such as SOX2, SOX4 and SOX9) in NSCLC, as well as their potential as diagnostic biomarkers and therapeutic targets, and the application of emerging technology in elucidating their functions. The present review aimed to provide a theoretical foundation for precision diagnostics and therapeutics to foster more effective NSCLC treatment.

Mebendazole (Mbz), a well‑known anthelminthic drug, has demonstrated anticancer properties in tumor models and patients, and is thus under consideration for repositioning into an anticancer drug. Mbz is directly cytotoxic in cell lines by various mechanisms and acts indirectly via immunomodulation. In the present study, the anticancer effects of Mbz, alone and in combination with cytotoxic drugs, were further characterized using primary cultures of patient tumor cells and the murine colon cancer cell line, CT26, and . Patient‑derived tumor cells from acute myeloid leukemia (AML) and ovarian, colorectal and renal cancer were exposed to Mbz alone and, for solid tumors and the CT26 cell line, in combination with irinotecan, cisplatin or gemcitabine (patient cells only). Cytotoxicity was assessed using the fluorometric microculture cytotoxicity assay. , the antitumor effects of Mbz and irinotecan, alone and in combination, were evaluated in the BALB/c CT26 colon cancer mouse model by tumor growth measurements and flow cytometric analysis of tumor immune cell infiltration. In the patient cell samples, Mbz showed modest single‑agent cytotoxicity, with the AML samples being the most sensitive, and displayed enhanced effects when combined with cytotoxic drugs, particularly irinotecan. CT26 cells showed modest dose‑independent sensitivity to Mbz, which enhanced the effect of both cisplatin and irinotecan. , Mbz and irinotecan both inhibited tumor growth, but the combination did not significantly outperform Mbz alone. Flow cytometry of the resected mouse tumors indicated that Mbz promoted macrophage polarization from the M2 to M1 phenotype, suggesting that immune modulation may contribute to its anticancer effect. Mbz has features making it a candidate for repositioning into an anticancer drug and part of its effect may be mediated by macrophage modulation.

Pancreatic ductal adenocarcinoma (PDAC) resistance to oxaliplatin is associated with diminished drug uptake and a poor molecular apoptotic response; however, the relative contribution of each of these modes of resistance remains unclear. Accordingly, PDAC cell lines (AsPC‑1 and BxPC‑3) and human patient‑derived organoids (hPDOs; h08 and h19) were assessed in the present study, with proliferation assays, atomic absorption spectroscopy‑based quantification of intracellular oxaliplatin, luminogenic caspase 3/7 assays, PCR array‑based transcriptomic analysis and RNA sequencing performed to scrutinize the oxaliplatin resistance phenotype. Notably, AsPC‑1 cells [half maximal inhibitory concentration (IC), 88.8±45 µM were 4.2‑fold more oxaliplatin resistant than BxPC‑3 cells (IC, 21±0.7 µM; P=0.02)]. In addition, when normalized to intracellular platinum levels, AsPC‑1 cells remained 2.5‑fold more resistant than BxPC‑3 (the fold difference was decreased by 40% from 4.2‑fold to 2.5‑fold; P=0.21). In hPDOs, resistant h19 took up oxaliplatin 22% less efficiently than sensitive h08, and the nominal resistance difference was 3.5‑fold, and it remained at 2.8‑fold after controlling for drug accumulation (the fold difference was decreased by 20% from 3.5‑fold to 2.8‑fold; P=0.34). These findings indicated that diminished drug uptake non‑significantly contributed to oxaliplatin resistance, which was in agreement with the rather minor differences in drug transporter expression levels (including and ). Furthermore, when challenged with identical intracellular oxaliplatin levels, AsPC‑1 cells exhibited delayed caspase 3/7 activity initiation, weaker induction of pro‑apoptotic genes (1.7‑fold vs. 5‑fold) and (2.5‑fold vs. 6‑fold), but stronger enhancement of anti‑apoptotic expression (7‑fold vs. 3‑fold) than BxPC‑3 cells. Taken together, oxaliplatin resistance in PDAC models may be highly linked to a poor apoptotic response, whereas drug uptake seems to be of minor relevance.