Search Results (13,476)

Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes, most patients do not respond to treatment or fail to achieve durable responses. Histone deacetylase inhibitors (HDACi) have emerged as promising immunomodulatory agents, with the potential to sensitize tumors to ICIs. We investigated the immunomodulatory effects of entinostat, a class I HDACi, in combination with dual ICI (anti-PD-1 and anti-CTLA-4) as well as with T-cell receptor (TCR) engineered T cells in preclinical NSCLC models. Methods: We employed human NSCLC cell lines and the immunogenic KRASG12D/p53-mutant KPN1.1 murine NSCLC cell line. In vitro, we assessed entinostat-induced changes in MHC class I and PD-L1 expression. In addition, we evaluated the effects of entinostat on a KRASG12D-specific TCR. In vivo, therapeutic efficacy and immune modulation were assessed by transplanting KPN1.1 cells subcutaneously and orthotopically into immunocompetent mice, followed by treatment with dual ICI, with or without entinostat. Immune populations in the spleen and blood were subsequently analyzed. Results: In vitro, entinostat induced the upregulation of MHC-I and PD-L1 expression in both human and murine NSCLC cell lines. In addition, entinostat treatment significantly enhanced antigen-specific tumor recognition and killing by T cells engineered to express a KRASG12D-specific TCR. In vivo, the addition of entinostat to dual immune checkpoint inhibition showed an incremental trend toward improved tumor growth control. Notably, entinostat plus dual ICI enhanced systemic immune activation, increasing circulating and splenic T-cell populations and significantly expanding both antigen-specific and overall effector CD8⁺ T cells. Consistently, the ex vivo co-culture of splenocytes from KPN1.1-bearing mice with KPN1.1 tumor cells demonstrated enhanced CD8⁺ antigen-specific T-cell recognition. Conclusions: In human and murine NSCLC models, entinostat potentiates TCR- and ICI-mediated tumor recognition through tumor-intrinsic and systemic immune modulation. These effects were reflected by increased MHC-I expression, expansion of antigen-specific effector CD8⁺ T cells, and enhanced CD8⁺ T-cell tumor recognition. These findings support a further evaluation of entinostat as a strategy to improve immunotherapy efficacy in NSCLC. Full article

Iron is essential for normal cellular function, but its dysregulation is increasingly recognized as a key factor in colorectal tumorigenesis. This review provides an integrated overview of iron-related biomarkers across the full spectrum of colorectal neoplasia, from preneoplastic lesions to advanced colorectal cancer (CRC). Evidence suggests that alterations in iron metabolism begin early, at the level of colorectal adenomas, where increased iron uptake and impaired export contribute to local iron accumulation and oxidative stress. As lesions progress to carcinoma, this imbalance becomes more pronounced, leading to expansion of the intracellular labile iron pool and supporting tumor growth, metabolic adaptation, and genomic instability. At the systemic level, patients often exhibit reduced circulating iron despite preserved or elevated ferritin levels, reflecting inflammation-driven functional iron deficiency. This pattern is largely mediated by dysregulation of the hepcidin–ferroportin axis. In this context, transferrin saturation and soluble transferrin receptor may provide a more accurate assessment of iron availability than ferritin alone. At the tissue level, increased expression of iron import proteins and impaired iron export promote intracellular iron retention. Excess iron further contributes to reactive oxygen species generation, leading to damage of DNA, lipids, and proteins. Clinically, iron-related biomarkers show variable diagnostic performance but may offer prognostic value. Integrating systemic and tissue biomarkers could improve risk stratification and support personalized approaches across the CRC continuum. Full article

Treatment-induced neuroendocrine prostate cancer (t-NEPC) is the major form of resistance to androgen receptor signaling inhibitors (ARSI) in advanced prostate cancer, characterized by pronounced invasiveness and lineage plasticity. Through in-depth analysis of prostate cancer cohorts, we found that glutamate ionotropic receptor kainate (GRIK) family members, specifically GRIK2 and GRIK5, are highly expressed in neural lineage plastic prostate cancer cells, NEPC patient-derived xenografts (PDX), and NEPC patient samples. Their expression positively correlates with neuroendocrine markers and inversely correlates with androgen receptor (AR) activity. Additionally, functional analyses indicated that AR has a direct transcriptional inhibitory effect on GRIK2 and GRIK5, and the absence of AR signaling leads to the upregulation of GRIK2 and GRIK5. Further RNA sequencing analysis revealed that GRIK5 silencing reprograms the cellular transcriptome, resulting in significant downregulation of AR signaling and fatty acid metabolism, while simultaneously activating immune and inflammatory responses in enzalutamide-resistant prostate cancer cells. In both cell line and NEPC PDX organoid models, loss of GRIK5 impaired proliferation and clonogenic growth. Notably, GRIK5 also contributes to enzalutamide resistance. Pharmacological evaluation revealed that Pan-GRIK antagonists exhibit anti-tumor activity, although the required relatively high concentrations suggest that more potent therapeutic strategies should be developed. Collectively, this study establishes that GRIK family members play critical roles in enzalutamide resistance and NEPC progression, highlighting GRIK signaling as a potential therapeutic target for overcoming lineage plasticity in prostate cancer. Full article

Ovarian cancer (OVC) is a leading cause of gynecological cancer mortality due to late-stage diagnosis and chemoresistance. Among the multiple molecular mediators, oncogenic epidermal growth factor receptor (EGFR) signaling has emerged as a key regulator of tumor progression and drug resistance, ultimately governing cancer survival. Therefore, this review focused on the molecular mechanisms of aberrant EGFR signaling to promote chemoresistance in ovarian cancer through multiple interlinking pathways, including the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascades. These pathways act in concert to confer resistance, including proliferation, antiapoptotic effects, cancer stem cell maintenance, and facilitating epithelial-mesenchymal transition (EMT), which function together to decrease sensitivity towards platinum-based and taxane chemotherapies. Furthermore, we incorporate novel evidence regarding EGFR cross-talk with extracellular matrix (ECM) and metabolic reprogramming, especially their relevance to immune evasion mechanisms, hypoxia, and extracellular vesicles (EVs)-mediated signaling. In addition, we elaborated on the limitation of the current EGFR targeting therapy, which will be beneficial for further designing new combinatorial treatment approaches by using EGFR inhibitors with immunotherapy, nanocarriers, and microbiota modulators. Overall, this review highlights the updated role of EGFR signaling as a key regulator of chemoresistance in ovarian cancer, providing insights for developing targeted therapies to overcome drug resistance and improve patient survival. Full article

Tumor microenvironment influences the process of tumorigenesis, with hypoxia being a characteristic of many solid tumors and an adverse prognostic factor. Carbonic anhydrases (CAs) are highly efficient zinc-containing enzymes that are overexpressed in many cancers, particularly under acidic and hypoxic conditions. CA IX expression promotes cancer cell proliferation, migration, and invasion. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a tyrosine transmembrane (ΤΜ) protein regulating embryonic development, angiogenesis, tissue homeostasis and cancer. Blocking VEGFR-2 signaling is one of the most promising approaches to hindering angiogenesis and growth of cancer cells. The epidermal growth factor receptor (EGFR) is a member of the ERBB family of receptor tyrosine kinases and plays a key role in cancer progression. EGFR is uniquely found in some brain, lung and other cancers. Development of novel strategies to regulate these factors is important for the treatment of tumors. Multifunctional drugs that act on multiple pathways offer a promising approach, improving therapeutic effectiveness while reducing side effects. The present review focuses on novel compounds that inhibit CA IX and target VEGFR-2 or EGFR. Full article

Marine medicinal algae represent a valuable reservoir of bioactive metabolites for anticancer drug discovery, yet the efficient identification of target-relevant compounds from chemically complex marine matrices remains challenging. In this study, an integrated cathepsin B-oriented strategy was developed to discover, prioritize, isolate, and validate antitumor metabolites from the brown alga Sargassum polycystum. Affinity ultrafiltration LC-MS was first applied to screen CTSB-binding constituents from the crude extract, followed by molecular docking, molecular dynamics simulation, and gray relational analysis for multidimensional candidate prioritization. Seven CTSB-binding metabolites were characterized, including chlorogenic acid, caffeic acid, cynarin, loliolide, taxifolin, senkyunolide H, and dihydroactinidiolide, with binding degrees of 73.99–85.61% at 2.5 U/mL CTSB. Molecular docking showed predicted binding affinities ranging from −6.3 to −9.4 kcal/mol, compared with −10.2 kcal/mol for the positive control CA-074Me. Integrated computational and biological evaluation identified caffeic acid, cynarin, and taxifolin as the top-ranked candidates. Preparative recovery was then achieved using counter-current chromatography combined with semi-preparative HPLC, and the isolated compounds were structurally identified by LC-MS/MS and NMR. Cellular assays in NCI-H1975 cells suggested that these metabolites reduced CTSB-associated enzymatic activity and intracellular CTSB-related fluorescence signals to different extents, with phenolic acid-type compounds exhibiting comparatively stronger effects. At the extract level, S. polycystum dose-dependently suppressed NCI-H1975 xenograft tumor growth, with inhibition rates of 48.78%, 36.58%, and 22.86% in the high-, middle-, and low-dose groups, respectively, without evident hepatorenal histopathological toxicity. This effect was associated with reduced CTSB, Ki-67, and Bcl-2 staining, increased Bax staining, enhanced apoptosis, and ultrastructural alterations in tumor tissues. Overall, this study provides a practical CTSB-oriented workflow for discovering antitumor metabolites from marine medicinal algae and supports further investigation of S. polycystum as a potential source of anti-NSCLC candidates. Full article

Background: Obesity is associated with aggressive prostate cancer, but the links between metabolic dysregulation, inflammation, adipocyte-associated signaling, and tumor growth remain incompletely defined. This study examined whether high-fat diet (HFD)-associated systemic changes and adipocyte-derived paracrine interactions are linked to prostate cancer growth in preclinical models. Methods: An HFD xenograft model and adipocyte co-culture systems were used to evaluate systemic and local tumor-supportive features. Pharmacologic/nutritional modulation was tested using green tea or EGCG, arctigenin, and the CCR2 antagonist RS 504393, alone or in combination. Tumor growth, cell proliferation, angiogenesis-related features, circulating metabolic and cytokine levels, and selected tumor-associated signaling proteins were analyzed. Results: HFD feeding was associated with increased circulating free fatty acids, IGF-1, MCP-1, IL-6, and VEGF, together with increased tumor growth, Ki67 staining, and CD31-positive microvessel density. Adipocyte co-culture systems were used to evaluate treatment-associated changes in prostate cancer cell proliferation under adipocyte-associated conditions. Combined modulation with green tea/EGCG, arctigenin, and RS 504393 was associated with greater reductions in adipocyte-associated proliferation, tumor growth, Ki67 staining, and CD31-positive microvessel density than single or dual interventions. Antibody array analysis showed treatment-associated changes in selected stress- and apoptosis-related proteins, including cleaved caspase-7 and phosphorylated Chk1. Conclusions: HFD-associated metabolic and inflammatory alterations, adipocyte-associated interactions, proliferative activity, angiogenesis-related features, and stress/apoptosis-related signaling changes were linked within a tumor-supportive framework in preclinical prostate cancer models. Combined pharmacologic/nutritional modulation was associated with reduced tumor-supportive features under HFD conditions. Further mechanistic and translational validation is needed. Full article

Background: Cancer-related cachexia is primarily characterized by systemic inflammation and progressive muscle wasting, which is why a high-protein diet (from 1.2 to 1.5 g/kg/day) is commonly recommended. However, concerns remain that an excessive supply of amino acids could promote tumor growth due to the metabolic flexibility of cancer cells, thereby favoring proliferation and survival. Systematic evidence addressing these concerns under controlled conditions for various types of cancer cells remains limited and inconclusive. Methods: We investigated the short-term effects of all 20 amino acids at both moderate (2×) and high (10×) concentrations to evaluate three key oncological endpoints in four human cancer cell lines: MDA-MB-231 (breast), HT29 (colorectal), PC3 (prostate), and PANC-1 (pancreatic). Cell proliferation was assessed by BrdU incorporation, metabolic activity by WST-1 assay, and apoptosis signaling by caspase-3/7 activity measurement. Results: Amino acid supplementation was not associated with a significant change in proliferation at either concentration across all four cell lines studied. Metabolic activity showed only minor variations throughout, with PC3 cells exhibiting slightly greater variability, although this did not reach statistical significance. Caspase-3/7 activity remained largely unchanged under all conditions; however, high-concentration lysine induced an approximately 2.5-fold increase in PANC1 cells, which was not statistically significant. Conclusions: These findings suggest that short-term exposure to individual amino acids, even at supraphysiological conditions, does not acutely enhance proliferative activity in the cancer cell lines studied, supporting the rationale for adequate protein and amino acid intake in patients with cancer cachexia. Full article

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide and is characterized by therapeutic resistance, metabolic plasticity, and immune evasion. Accumulating evidence indicates that metabolic reprogramming not only supports tumor growth but also creates exploitable vulnerabilities linked to regulated cell death. Traditional Chinese medicine (TCM)-derived small molecules have attracted increasing attention owing to their structural diversity, multitarget properties, and broad pharmacological activities. In this review, we summarize recent advances in TCM-derived compounds targeting metabolism-associated regulated cell death in NSCLC, with a primary focus on ferroptosis and a cautious discussion of emerging cuproptosis- and disulfidptosis-related mechanisms. Ferroptosis has been extensively investigated in this context, with natural compounds shown to induce cell death through coordinated regulation of cystine transport, glutathione metabolism, GPX4 activity, iron homeostasis, and lipid peroxidation. In parallel, emerging studies suggest that certain natural products may influence copper-dependent cell death pathways and metabolic states associated with disulfide stress. These processes are closely linked to distinct metabolic features of NSCLC, including lipid dependency, copper homeostasis, and glucose utilization. Finally, we discuss major challenges for clinical translation, including poor bioavailability, off-target toxicity, insufficient biomarker stratification, and limited high-quality evidence, and highlight emerging strategies such as nanodelivery systems, structural optimization, and targeted protein degradation approaches. Overall, TCM-derived small molecules represent a promising source of metabolism-targeted therapeutics and provide a foundation for further exploration of regulated cell death in NSCLC. Current evidence is strongest for ferroptosis induction, whereas cuproptosis- and disulfidptosis-related mechanisms remain emerging areas that require further experimental validation in NSCLC models. Full article

Backgrounds: Bladder cancer shows pronounced biological heterogeneity that underlies its variable clinical course and prognosis. Our study aims to delineate clinically relevant differences in bladder cancer using an immunohistochemistry-based molecular subtyping approach. Methods: This retrospective study included 590 patients with bladder cancer treated at a single center. Tumors were stratified into luminal versus non-luminal categories according to CK20, GATA3, CK5/6, and CK14. Associations between molecular subtype, histopathological growth patterns, pathological response to neoadjuvant chemotherapy (NAC), and clinical survival endpoints were analyzed. Overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) were evaluated through Kaplan–Meier survival curves together with Cox proportional hazards regression analyses. Results: Non-luminal tumors exhibited significantly more aggressive pathological growth patterns, including higher levels of tumor budding (p = 0.002), a predominance of non-cohesive or spindle/single-cell architecture (p = 0.003), and more frequent disseminated spreading patterns (p = 0.001), whereas luminal tumors more commonly displayed a higher frequency of tertiary lymphoid structures (TLSs; p = 0.041). Among patients receiving NAC, non-luminal tumors achieved a significantly higher pathological complete response (pCR) rate compared with luminal tumors (p = 0.007), while no significant inter-subtype difference was detected in pathological downstaging between subtypes (p = 0.126). Despite inferior pathological response, luminal tumors demonstrated significantly improved OS (p = 0.003), RFS (p = 0.002) and PFS (p < 0.001) compared with non-luminal tumors. In multivariable Cox regression analysis, molecular subtype was identified as an independent predictor of OS, with luminal tumors showing a lower mortality risk (HR = 0.51, 95% CI 0.33–0.79, p = 0.003). Conclusions: These findings indicate that pathological response and long-term survival follow distinct, subtype-dependent trajectories in bladder cancer. Favorable pathological response does not necessarily correspond to improved long-term survival across molecular subtypes. Full article

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) representing the most common subtype. Despite major advances in immunotherapy, only a subset of patients benefits from current treatments, highlighting the need to better understand the tumor immune microenvironment (TIME) and the mechanisms underlying immune escape. In this context, extracellular vesicles (EVs) have emerged as key mediators of intercellular communication in lung cancer. This review summarizes the current knowledge on the role of EVs in NSCLC progression and immune regulation. We discuss how EVs contribute to primary tumor growth, dissemination, and pre-metastatic niche formation through the transfer of proteins, metabolites and nucleic acids. Particular attention is given to EV-mediated modulation of immune cells, highlighting their role in both immune suppression and immune activation. Furthermore, we provide an overview of the emerging therapeutic applications of EVs in lung cancer, including their use as drug-delivery systems and immunotherapeutic platforms. Full article

Background and Objectives: Sevoflurane, a widely used inhalational anesthetic, is frequently administered during hepatocellular carcinoma (HCC) surgery, including hepatic resection and orthotopic liver transplantation. Because such procedures often require prolonged anesthetic exposure, the potential influence of sevoflurane on HCC cell behavior is of clinical interest. We aimed to evaluate the effects of sevoflurane on the proliferation and migration of HepG2 cells in vitro and on tumor growth in a xenograft mouse model in vivo, and to explore whether hypoxia-inducible factor-1α (HIF-1α) might be involved in this process. Materials and Methods: For the in vitro experiments, HepG2 cells were exposed to room air (0%), 2%, or 4% sevoflurane. A scratch wound healing assay was used to assess cell migration, and the number of viable cells was quantified by hemocytometer counting on day 4 to estimate proliferation. For the in vivo experiments, BALB/c nude mice bearing HepG2 xenografts were exposed to room air, 2% sevoflurane, or 4% sevoflurane for 3 h, three times weekly for 5 weeks. Tumor size and tumor weight were measured at the end of the exposure period. HIF-1α protein levels in tumor tissue were measured by enzyme-linked immunosorbent assay (ELISA) in tumor lysates and normalized to total tumor protein as an exploratory mechanistic analysis. Given the small sample available for this endpoint, the analysis had limited sensitivity to detect modest differences. Results: When wound closure was quantified and pooled across the analyzable experiments, no statistically significant difference was detected among the room air, 2% sevoflurane, and 4% sevoflurane groups (day-2 closure 19.9 ± 32.1%, 22.1 ± 25.8%, and 22.3 ± 28.8%, respectively; repeated-measures ANOVA p = 0.82), with variability dominated by between-experiment rather than treatment differences. In the proliferation assay, the number of viable HepG2 cells on day 4 was significantly lower in the 2% sevoflurane group (62.6 ± 3.3 × 10⁵) than in the room air group (68.5 ± 4.2 × 10⁵; p < 0.05); the 4% sevoflurane group (66.0 ± 3.2 × 10⁵) showed an intermediate value that did not reach statistical significance. In the xenograft model, mean tumor size in the room air, 2% sevoflurane, and 4% sevoflurane groups was 7.1 ± 1.9, 2.7 ± 2.0, and 2.1 ± 0.9 cm³, respectively (p = 0.041 for room air vs. 2% sevoflurane; p = 0.034 for room air vs. 4% sevoflurane). Tumor weight was likewise lower in the sevoflurane groups (room air, 7.88 ± 2.2 g; 2% sevoflurane, 2.95 ± 2.1 g; 4% sevoflurane, 2.3 ± 1.6 g; p = 0.044 for room air vs. 2% sevoflurane; p = 0.067 for room air vs. 4% sevoflurane). No statistically significant differences in tumor HIF-1α protein levels were observed among the three groups. Conclusions: In this exploratory study, sevoflurane exposure was associated with reduced HepG2 xenograft tumor growth in vivo, whereas its in vitro effects were more limited: a reduction in viable cell number was observed only at 2% sevoflurane, and an effect on cell migration could not be confirmed when analyzed across experiments. Tumor HIF-1α levels did not differ significantly between groups, suggesting that other molecular pathways may be involved. Further mechanistic and clinical studies are warranted before any conclusions can be drawn about the relevance of these findings to the perioperative management of patients with HCC. Full article

Background and Objectives: A subset of cancer patients treated with immune checkpoint inhibitors may experience rapid tumor progression rather than therapeutic benefit, a phenomenon described as hyperprogressive disease (HPD), which is linked to poor prognosis and shortened survival. Reliable biomarkers capable of predicting HPD remain lacking. To better understand the molecular background of HPD, we analyzed promoter region methylation and somatic mutation profiles in cancer-related genes in patients with malignant melanoma (MM) and renal cell carcinoma (RCC) undergoing anti-PD-1/PD-L1 treatment. Methods: Patients diagnosed with MM or RCC and treated with anti-PD-1/PD-L1 agents between 2011 and 2020 were included, and FFPE tumor samples along with paired normal tissues were analyzed. A diagnosis of HPD was assigned to patients with RECIST 1.1-defined progressive disease who demonstrated a ≥2-fold acceleration in tumor growth kinetics after initiation of immune checkpoint inhibitor therapy. Methylation-specific real-time PCR was performed on 54 samples (15 MM tumors, 22 RCC tumors, 17 RCC-matched adjacent normal samples) to assess promoter methylation of PIK3CA, BAP1, PTEN, and TP53. Next-generation sequencing (NGS) with an 86-gene pan-cancer panel was conducted on 9 HPD samples. Results: Promoter hypermethylation involving PIK3CA, BAP1, PTEN, and TP53 was more pronounced in HPD-associated tumor samples (n = 16) than in tumors without HPD (n = 21). Within the MM cohort, PTEN and TP53 methylation levels demonstrated statistically significant differences between the two groups (p = 0.005 and p = 0.028, respectively), while no comparable associations were observed in RCC patients. NGS analysis detected missense mutations classified as pathogenic or likely pathogenic in 5 of 9 HPD patients (55.6%), involving KIT, PTEN, and VHL. Conclusions: Promoter region hypermethylation in cancer-related genes may contribute to the aggressive tumor behavior observed in HPD. The somatic variants identified in HPD patients are consistent with known oncogenic pathways. These findings support further investigation of epigenetic and genomic biomarkers for HPD risk stratification in larger, prospective cohorts. Full article

The biggest challenge faced by classical anticancer therapy is drug resistance, which causes cancer recurrence and metastasis. Two underlying mechanisms could be responsible, including the stemness of pro-survival autophagy-associated cancer stem cells (CSCs). Background/Objectives: The relationship between CSCs and autophagy in gynecological cancer is still unknown. However, it has been shown that CSCs’ in vitro self-renewal ability is decreased when autophagy is inhibited. Helping to maintain normal tissue homeostasis, autophagy is a catabolic process involved in degrading long-lived proteins and cytoplasmic organelles. Autophagy acts as a key player in the human body’s self-regenerating tissues. It also has a reproductive function, contributing to decidualization for a successful pregnancy. The aim of our review is to identify similarities and differences between these processes, using these findings to discover new therapeutic strategies through nanotechnology. Method: We conducted a narrative review, identifying heterogeneity in the data in the literature, and found 153 relevant articles. Discussions: While autophagy has been proven to be capable of acting as a tumor suppressor, it also promotes tumor progression. Moreover, it has been linked to cancer stem cell regulation, therapy resistance, cancer invasion, and metastasis. Several molecular mechanisms have been linked to autophagy. Remarkably, some cellular processes required for proper placentation, including autophagy, are common between placental development and tumor growth. Just as trophoblast cells invade and migrate, so do cancer cells. While in the trophoblast, this phenomenon is programmed and controlled; in cancer, this regulation is lost. As shown, we thus observed commonalities and discrepancies in the phenotypes and underlying molecular mechanisms of autophagy regulation in preeclampsia versus cancer contexts. Translational applicability of nanomedicine research strategies and design paradigms between preeclampsia intervention and cancer therapy has been sought. Conclusions: Autophagy-based nanotechnology seems to be feasible in both placental ischemia in preeclampsia and cancers. This review draws parallels between targeted treatments in malignancies and placenta-derived PE. Comparing these diseases provides a novel molecular rationale and the possibility of identifying treatment through autophagy modulation. Full article