Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n = 151) and plasma-derived (n = 120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer. Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.

Unshielding Exosomal RNA Unleashes Tumor Growth And Metastasis.

Reciprocal interactions between tumor cells and their microenvironment drive cancer progression and therapy resistance. In this issue, Nabet et al. demonstrate that dynamic feedback between tumor and stroma subverts normal inflammatory responses by triggering the release of exosomes containing unshielded RNAs that activate pattern recognition receptors, thereby promoting tumor growth and metastasis.

Tumour extracellular vesicles and particles induce liver metabolic dysfunction.

Cancer alters the function of multiple organs beyond those targeted by metastasis1,2. Here we show that inflammation, fatty liver and dysregulated metabolism are hallmarks of systemically affected livers in mouse models and in patients with extrahepatic metastasis. We identified tumour-derived extracellular vesicles and particles (EVPs) as crucial mediators of cancer-induced hepatic reprogramming, which could be reversed by reducing tumour EVP secretion via depletion of Rab27a. All EVP subpopulations, exosomes and principally exomeres, could dysregulate hepatic function. The fatty acid cargo of tumour EVPs-particularly palmitic acid-induced secretion of tumour necrosis factor (TNF) by Kupffer cells, generating a pro-inflammatory microenvironment, suppressing fatty acid metabolism and oxidative phosphorylation, and promoting fatty liver formation. Notably, Kupffer cell ablation or TNF blockade markedly decreased tumour-induced fatty liver generation. Tumour implantation or pre-treatment with tumour EVPs diminished cytochrome P450 gene expression and attenuated drug metabolism in a TNF-dependent manner. We also observed fatty liver and decreased cytochrome P450 expression at diagnosis in tumour-free livers of patients with pancreatic cancer who later developed extrahepatic metastasis, highlighting the clinical relevance of our findings. Notably, tumour EVP education enhanced side effects of chemotherapy, including bone marrow suppression and cardiotoxicity, suggesting that metabolic reprogramming of the liver by tumour-derived EVPs may limit chemotherapy tolerance in patients with cancer. Our results reveal how tumour-derived EVPs dysregulate hepatic function and their targetable potential, alongside TNF inhibition, for preventing fatty liver formation and enhancing the efficacy of chemotherapy.

Reprogramming anchorage dependency by adherent-to-suspension transition promotes metastatic dissemination.

BACKGROUND: Although metastasis is the foremost cause of cancer-related death, a specialized mechanism that reprograms anchorage dependency of solid tumor cells into circulating tumor cells (CTCs) during metastatic dissemination remains a critical area of challenge. METHODS: We analyzed blood cell-specific transcripts and selected key Adherent-to-Suspension Transition (AST) factors that are competent to reprogram anchorage dependency of adherent cells into suspension cells in an inducible and reversible manner. The mechanisms of AST were evaluated by a series of in vitro and in vivo assays. Paired samples of primary tumors, CTCs, and metastatic tumors were collected from breast cancer and melanoma mouse xenograft models and patients with de novo metastasis. Analyses of single-cell RNA sequencing (scRNA-seq) and tissue staining were performed to validate the role of AST factors in CTCs. Loss-of-function experiments were performed by shRNA knockdown, gene editing, and pharmacological inhibition to block metastasis and prolong survival. RESULTS: We discovered a biological phenomenon referred to as AST that reprograms adherent cells into suspension cells via defined hematopoietic transcriptional regulators, which are hijacked by solid tumor cells to disseminate into CTCs. Induction of AST in adherent cells 1) suppress global integrin/ECM gene expression via Hippo-YAP/TEAD inhibition to evoke spontaneous cell-matrix dissociation and 2) upregulate globin genes that prevent oxidative stress to acquire anoikis resistance, in the absence of lineage differentiation. During dissemination, we uncover the critical roles of AST factors in CTCs derived from patients with de novo metastasis and mouse models. Pharmacological blockade of AST factors via thalidomide derivatives in breast cancer and melanoma cells abrogated CTC formation and suppressed lung metastases without affecting the primary tumor growth. CONCLUSION: We demonstrate that suspension cells can directly arise from adherent cells by the addition of defined hematopoietic factors that confer metastatic traits. Furthermore, our findings expand the prevailing cancer treatment paradigm toward direct intervention within the metastatic spread of cancer.

Importance of Local Ablative Therapies for Lung Metastases in Patients With Colorectal Cancer.

OBJECTIVE: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy. SUMMARY BACKGROUND DATA: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC. METHODS: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered. RESULTS: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased. CONCLUSIONS: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period.

Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study - (NCT05103020) - study protocol.

BACKGROUND: Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis. METHODS: This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate. DISCUSSION: This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.

Bleeding risk and mortality according to antithrombotic agents' exposure in cancer-related stroke patients: nationwide population-based cohort study in South Korea.

BACKGROUND: Ischemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial. METHODS: Subjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used. RESULTS: Two thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval [CI], 1.20-1.52; p < 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13-2.09; p = 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47-2.00; p < 0.001). CONCLUSIONS: Bleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug.

Antioxidant Iron Oxide Nanoparticles: Their Biocompatibility and Bioactive Properties.

A lot of nanomaterials have been applied to various nano-biotechnological fields, such as contrast agents, drug or gene delivery systems, cosmetics, and so on. Despite the expanding usage of nanomaterials, concerns persist regarding their potential toxicity. To address this issue, many scientists have tried to develop biocompatible nanomaterials containing phytochemicals as a promising solution. In this study, we synthesized biocompatible nanomaterials by using gallic acid (GA), which is a phytochemical, and coating it onto the surface of iron oxide nanoparticles (IONPs). Importantly, the GA-modified iron oxide nanoparticles (GA-IONPs) were successfully prepared through environmentally friendly methods, avoiding the use of harmful reagents and extreme conditions. The presence of GA on the surface of IONPs improved their stability and bioactive properties. In addition, cell viability assays proved that GA-IONPs possessed excellent biocompatibility in human dermal papilla cells (HDPCs). Additionally, GA-IONPs showed antioxidant activity, which reduced intracellular reactive oxygen species (ROS) levels in an oxidative stress model induced by hydrogen peroxide (H2O2). To investigate the impact of GA-IONPs on exosome secretions from oxidative stress-induced cells, we analyzed the number and characteristics of exosomes in the culture media of HDPCs after H2O2 stimulation or GA-IONP treatment. Our analysis revealed that both the number and proportions of tetraspanins (CD9, CD81, and CD63) in exosomes were similar in the control group and the GA-IONP-treated groups. In contrast, exosome secretion was increased, and the proportion of tetraspanin was changed in the H2O2-treated group compared to the control group. It demonstrated that treatment with GA-IONPs effectively attenuated exosome secretion induced by H2O2-induced oxidative stress. Therefore, this GA-IONP exhibited outstanding promise for applications in the field of nanobiotechnology.

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings. METHODS: This was a multicentre retrospective analysis. Between May 2020 and February 2021, 138 patients received Ate/Bev as first-line treatment for advanced HCC from 11 institutions. We excluded patients with Child-Pugh B or C and BCLC D stage, and the remaining 121 patients were included in this analysis. RESULTS: According to RECIST 1.1, the objective response and disease control rates were 24.0% and 76.0%. The median follow-up duration was 5.9 months (95% confidence interval [CI], 5.4-6.4), the median progression-free survival (PFS) was 6.5 months (95% CI, 4.1-9.0), and median overall survival (OS) was not reached (95% CI, not available). The most frequent grade 3-4 adverse event was aspartate aminotransferase elevation (10.7%). In the multivariate analyses, AFP increase (P = .037), baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 5 (P = .023), and best response to stable disease or progressive disease (P = .019) were significantly associated with worse PFS. Macrovascular invasion (P = .048) and baseline NLR ≥5 (P < .001) were significantly associated with worse OS. CONCLUSIONS: Ate/Bev showed real-life efficacy and safety in Korean patients with advanced HCC, in line with results from phase III trial. Considering unfavourable survival outcomes of Ate/Bev in patients with elevated NLR, careful assessment of treatment response needs to be performed in this group.

Magnetofluoro-Immunosensing Platform Based on Binary Nanoparticle-Decorated Graphene for Detection of Cancer Cell-Derived Exosomes.

Multi-functionalized carbon nanomaterials have attracted interest owing to their excellent synergic properties, such as plasmon resonance energy transfer and surface-enhanced Raman scattering. Particularly, nanoparticle (NP)-decorated graphene (GRP) has been applied in various fields. In this study, silver NP (AgNP)- and magnetic iron oxide NP (IONP)-decorated GRP were prepared and utilized as biosensing platforms. In this case, AgNPs and GRP exhibit plasmonic properties, whereas IONPs exhibit magnetic properties; therefore, this hybrid nanomaterial could function as a magnetoplasmonic substrate for the magnetofluoro-immunosensing (MFI) system. Conversely, exosomes were recently considered high-potential biomarkers for the diagnosis of diseases. However, exosome diagnostic use requires complex isolation and purification methods. Nevertheless, we successfully detected a prostate-cancer-cell-derived exosome (PC-exosome) from non-purified exosomes in a culture media sample using Ag/IO-GRP and dye-tetraspanin antibodies (Ab). First, the anti-prostate-specific antigen was immobilized on the Ag/IO-GRP and it could isolate the PC-exosome from the sample via an external magnetic force. Dye-tetraspanin Ab was added to the sample to induce the sandwich structure. Based on the number of exosomes, the fluorescence intensity from the dye varied and the system exhibited highly sensitive and selective performance. Consequently, these hybrid materials exhibited excellent potential for biosensing platforms.

Targeting mutant KRAS with CRISPR-Cas9 controls tumor growth.

KRAS is the most frequently mutated oncogene in human tumors, and its activating mutations represent important therapeutic targets. The combination of Cas9 and guide RNA from the CRISPR-Cas system recognizes a specific DNA sequence and makes a double-strand break, which enables editing of the relevant genes. Here, we harnessed CRISPR to specifically target mutant KRAS alleles in cancer cells. We screened guide RNAs using a reporter system and validated them in cancer cells after lentiviral delivery of Cas9 and guide RNA. The survival, proliferation, and tumorigenicity of cancer cells in vitro and the growth of tumors in vivo were determined after delivery of Cas9 and guide RNA. We identified guide RNAs that efficiently target mutant KRAS without significant alterations of the wild-type allele. Doxycycline-inducible expression of this guide RNA in KRAS-mutant cancer cells transduced with a lentiviral vector encoding Cas9 disrupted the mutant KRAS gene, leading to inhibition of cancer cell proliferation both in vitro and in vivo. Intra-tumoral injection of lentivirus and adeno-associated virus expressing Cas9 and sgRNA suppressed tumor growth in vivo, albeit incompletely, in immunodeficient mice. Expression of Cas9 and the guide RNA in cells containing wild-type KRAS did not alter cell survival or proliferation either in vitro and in vivo. Our study provides a proof-of-concept that CRISPR can be utilized to target driver mutations of cancers in vitro and in vivo.

Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck.

BACKGROUND: Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs). METHODS: Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab. RESULTS: For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone. CONCLUSIONS: The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN. CLINICAL TRIAL REGISTRATION: NCT01527877.

Prognosis of Synchronous Colorectal Liver Metastases After Simultaneous Curative-Intent Surgery According to Primary Tumor Location and KRAS Mutational Status.

BACKGROUND: Tumor location and KRAS mutational status have emerged as prognostic factors of colorectal cancer. We aimed to define the prognostic impact of primary tumor location and KRAS mutational status among synchronous colorectal liver metastases (CRLM) patients who underwent simultaneous curative-intent surgery (SCIS). METHODS: We compared the clinicopathologic characteristics and long-term outcomes of 227 patients who underwent SCIS for synchronous CRLM, according to tumor location and KRAS mutational status. We cross-classified tumor location and KRAS mutational status and compared survival outcomes between the four resulting patient groups. RESULTS: Forty-one patients (18.1%) had right-sided (RS) tumors and 186 (81.9%) had left-sided (LS) tumors. One-third of tumors (78/227) harbored KRAS mutations. The KRAS mutant-type (KRAS-mt) was more commonly observed among RS tumors than among LS tumors [21/41 (51.2%) vs. 57/186 (30.6%), p = 0.012]. Median follow-up time was 43.4 months. Patients with RS tumors had shorter survival times than those with LS tumors [median disease-free survival (DFS): RS, 9.9 months vs. LS, 12.1 months, p = 0.003; median overall survival (OS): RS, 49.7 months vs. LS, 88.8 months, p = 0.039]. RS tumors were a negative prognostic factor for DFS [hazard ratio (HR) 1.878, p = 0.001] and OS (HR 1.660, p = 0.060). RS KRAS-mt and LS KRAS wild-type (KRAS-wt) tumors had the worst and best oncological outcomes, respectively. CONCLUSION: Tumor location has a prognostic impact in patients who underwent SCIS for CRLM, and RS KRAS-mt tumors yielded the worst oncological outcome. These results may allow for more tailored multimodality treatments.

Pre-screening of patient-reported symptoms using the Edmonton Symptom Assessment System in outpatient palliative cancer care.

OBJECTIVES: Although early palliative care is associated with a better quality of life and improved outcomes in end-of-life cancer care, the criteria of palliative care referral are still elusive. METHODS: We collected patient-reported symptoms using the Edmonton Symptom Assessment System (ESAS) at the baseline, first and second follow-up visits. A total of 71 patients were evaluable, with a median age of 65 years, male (62%) and Eastern Cooperative Oncology Group (ECOG) performance status distribution of 1/2/3 (28%/39%/33%) respectively. RESULTS: Twenty (28%) patients had moderate/severe symptom burden with the mean ESAS ≥ 5. Interestingly, most of the patients with moderate/severe symptom burdens (ESAS ≥ 5) had globally elevated symptom expression. While the mean ESAS score was maintained in patients with mild symptom burden (ESAS < 5; 2.7 at the baseline; 3.4 at the first follow-up; 3.0 at the second follow-up; p = .117), there was significant symptom improvement in patients with moderate/severe symptom burden (ESAS ≥ 5; 6.5 at the baseline; 4.5 at the first follow-up; 3.6 at the second follow-up; p < .001). CONCLUSIONS: In conclusion, advanced cancer patients with ESAS ≥ 5 may benefit from outpatient palliative cancer care. Pre-screening of patient-reported symptoms using ESAS can be useful for identifying unmet palliative care needs in advanced cancer patients.

Improvement of the Electrical Properties of a Cu(In,Ga)Se2 Solar Cell Based on a ZnS Buffer Layer from Radio Frequency Magnetron Sputtering.

We fabricated zinc sulfide (ZnS) buffer layers with a great band gap and small light loss at a short wavelength, and then applied them to copper indium gallium sulphur-selenide (CIGS) thin film solar cells. A CIGS evaporation system was used for fabrication of the CIGS thin films, and a thickness monitor was used to check the evaporation rate at each source. The evaporation rate and deposition time were adjusted to change the composition ratio of the thin films. Also, CIGS thin films were deposited by changing the temperature of the substrates from room temperature (RT) to 150 °C, 250 °C, and 350 °C during ZnS deposition, and among them, the optimal substrate temperature was selected to measure the light conversion efficiency of ZnS-deposited CIGS thin film solar cells. The grown ZnS thin films were analyzed for crystallinity and composition by using X-ray diffraction, and by using a scanning electron microscope, the cross section and surface shape of the thin films were examined. When we applied the ZnS thin film that was fabricated at a temperature of 150 °C with a thickness of 50 nm as a buffer layer for the CIGS solar cells, we obtained a light conversion efficiency of 14.48% without an antireflection layer.

Indium Zinc Oxide Thin-Film Transistors with Ultraviolet Post-Annealing Treatment.

Ultraviolet treatment (UV) light was performed for indium zinc oxide thin-film transistors (TFTs) for different time so as to study the effects of post-annealing on electrical characteristic of TFTs. Electrical characteristic results proved that the value of high mobility after UV post-annealing process (2 mW/cm². for 30 s was obviously enhanced, and it had an acceptable on/off ratio, reasonable threshold voltage, and subthreshold swing. Among them, the value of the electronic mobility is 2.41 cm²/Vs, the threshold voltage value is 8.31 V, the on/off current ratio value is 2×2 × 105, and the subthreshold swing value is 1.13 V/dec.

Capacitance-Voltage Characteristics Analysis of Indium Zinc Oxide Thin Film Transistors Based Ultraviolet Light Irradiation.

The mechanism of solution-processed indium zinc oxide (IZO) thin film transistors (TFTs) made by simultaneous spin coating and ultraviolet (UV) light irradiation was investigated by capacitance-voltage (C-V) measurement. The application of UV light on the IZO TFTs was found to improve the thin film surface structure, and pledge to receive low degree of roughness. Meanwhile, electrical characteristics indicated that the TFT prepared at the UV light irradiation with 90 s exhibits the best performance with field-effect mobility 5.6 cm²/Vs, threshold voltage ═ -0.13 V, subthreshold gate swing 0.64 V/decade and on/off ratio ═ 1.7 × 106. In the C-V contrastive analysis with different UV light irradiation time by 60 s and 90 s, the frequency was varied from 100 Hz to 10 kHz to investigate low as well as high frequency C-V.

High-Efficiency Cu(In,Ga)Se2 Thin Film Solar Cells Using ZnS and CdS Buffer Layers.

Most of the existing copper indium gallium diselenide (CIGS) thin film solar cells are based on a cadmium sulfide (CdS) buffer layer fabricated using a chemical bath deposition (CBD) process. However, due to environmental pollution caused by material toxicity and the unique wet process's incompatibility with the vacuum process, many studies are now being actively carried out on nontoxic buffer layers. In this study, to replace CdS buffer layers, zinc sulfide (ZnS) buffer layers with a big band gap and a low optical loss at a short wavelength were fabricated using a magnetron sputtering system. For comparative analysis, this study also fabricated CdS buffer layers using the CBD process. Then, the conversion efficiency of CIGS thin film solar cells deposited with ZnS and CdS thin film as buffer layers was measured. The light conversion efficiency of ZnS buffer layer-based CIGS was measured at 14.44%, while that of the CdS buffer layer-based CIGS was measured at 15.71%. Given that both are higher than the minimum conversion efficiency required for commercialization (10%), ZnS buffer layer-based solar cells could have a competitive edge over the existing CdS buffer layer-based solar cells.