Abstract: Background: Squamous cell carcinoma of the skin (SCC) is the second most common neoplasm in humans and the most frequent in Brazil (80% in the head and neck region, 20% mortality). Brazil is a world leader in organ transplants (more than 30,000 transplants in 2019). The risk of transplant patients (Tx) developing SCC is 65-250 times higher, with deeper infiltration, advanced stage, higher local recurrence, occult metastases and worse survival. Objective: To investigate the prognostic factors of locally advanced cutaneous squamous cell carcinoma (LASCC) of the head and neck region in transplant patients. Methods:16-year retrospective, single-center series of patients with LASCC in the head and neck region who underwent surgical treatment. Were analyzed: clinical and Tx data, clinical/pathological stage, surgical treatment, parotid/regional and distant metastases, recurrence and survival. Results: 156 patients were included: 69.2% women, 65.3 years; mean primary size: 4.24 cm, 66% T3/T4 tumors, 71% grade 2/3 differentiation, 20.5% transplant recipients, follow-up: 33.6 months. Most affected regions: malar/nasal (28.8%), auricular (19.2%). Surgeries: wide resection with reconstruction (58.9%), exenteration (14.1%), temporalectomy (11.5%). Univariate analysis: Recurrence: immunosuppressor drugs (p=0.009), transplanted (p=0.006), compromised margin (p=0.049), Mortality: immunosuppression (p=0.028), Total Resection and reconstruction (p=0.013), Stage(8ed) III-IV (p<0.001), compromised margin (p<0.001), neck metastasis with extranodal extension (p=0.018). Multivariate analysis: Recurrence: Transplanted HR:3.69 (p<0.001), Neck metastasis extranodal extension HR:5.41 (p<0.001), Evolution to Distant metastasis HR:5.27 (p<0.001); Mortality: Neck metastasis extranodal extension HR:1.94, (p=0.032), Compromised Margins HR:1.87 (p=0.001), Main Surgical Procedures: Temporalectomy HR:2.83 (p=0.007); Major Rhinectomy HR:2.47 (p=0.005); Worst Overall Survival: Tx compared to NonTx (p=0.069), Worst Survival with Recurrence: Tx compared to NonTx (p=0.005). Conclusions: The LASCC and Transplanted (immunosuppressed) group present low survival, worse prognosis, high risk of recurrence and mortality outcome, formulation of specific guidelines to standardize treatment and predict outcomes in this population are strictly necessary.

Abstract: (1) Background: MicroRNAs (miRNAs) are candidate biomarkers of therapeutic re-sponse; this study sequenced tumor miRNAs before and after neoadjuvant chemoradi-ation (CRT) in cohorts with locally advanced rectal cancer undergoing total mesorectal excision. (2) Materials and Methods: A total of 79 tumor samples, with 36 in the pre-operative (pre-OP) and 43 in the post-operative (post-OP) group, underwent miRNA profiling with the NanoString nCounter Human v3 assay and functional tar-get/pathway analysis using miRDB and TargetScanHuman. (3) Results: NanoString nCounter profiling of 798 miRNAs showed an overall higher expression in post-OP versus pre-OP samples, with 93 miRNAs upregulated in the post-OP group. Tar-get/pathway analyses of the top upregulated miRNAs indicated enrichment across 37 KEGG pathways—including MAPK and Ras signaling and proteoglycans in can-cer—and qRT-PCR validated significant post-OP increases in six miRNAs (miR-143-3p, miR-145-5p, miR-99a-5p, miR-125b-5p, miR-100-5p, and let-7c-5p). (4) Conclusion: We found and validated significant differentially expressed (DE) miRNAs in the post-OP group compared to the pre-OP group in patients with rectal cancer undergoing con-current CRT. These DE miRNAs might serve as the key molecules in CRT-induced suppression of tumor progression and immunomodulation. The further role of DE miRNAs as significant biomarkers needs to be explored in future studies.

Abstract:

Cadherin 13 (CDH13), also known as T-cadherin or H-cadherin, is a member of the cadherin superfamily. CDH13 is anchored to the plasma membrane via glycosylphosphatidylinositol. CDH13 plays an essential role in the development of the heart and nervous systems, including the brain. Many reports have identified CDH13 as a risk factor for neurodevelopmental disorders. Furthermore, CDH13 has been shown to be expressed in numerous cancers, but its role as a cancer-promoting or -suppressing factor remains unclear. Therefore, the development of highly sensitive and specific anti-CDH13 monoclonal antibodies (mAbs) is necessary to elucidate the biological and pathological functions of CDH13. In this study, we established a novel anti-human CDH13 mAb (clone Ca₁₃Mab-4) using the Cell-Based Immunization and Screening (CBIS) method. Ca₁₃Mab-4 can be used for flow cytometric analysis. Ca₁₃Mab-4 binds specifically to CDH13 and not to other cadherin family members. The dissociation constant values of Ca₁₃Mab-4 for CDH13-overexpressed CHO-K1 and U87MG glioma cells were determined as 2.5 (± 0.6) x 10^-8 M and 8.9 (± 2.1) x 10^-9 M, respectively. Furthermore, Ca₁₃Mab-4 clearly detected CDH13 in the western blot and immunohistochemistry of cell sections. Therefore, the Ca₁₃Mab-4, established by CBIS method, could be a valuable tool for basic research and is expected to contribute to elucidating the relationship between CDH13 and diseases, including neurodevelopmental disorders and cancer.

Abstract: Epithelial, endothelial and many connective tissue cells are normally attached to the extracellular matrix (ECM). These cells rely on the ECM for structural support, signaling, and regulation of their behavior. When these cells lose this attachment or are in an inappropriate location, they soon die by a mechanism called anoikis (homelessness). Anoikis, is a programmed cell death of apoptotic nature, however, in certain cases it can be overcome and detached cells can survive in the absence of the correct signals from the ECM. This is the case for malignant cells, where anoikis resistance is a prerequisite for invasion and metastasis. Without anoikis resistance (anchorage-independency), tumors would be unable to abandon their normal sites and invade neighboring tissues and metastasize at distant locations. Anoikis is the natural barrier against cancer progression. Therefore, overcoming anoikis is a major step in cellular transformation. Cancer cells have developed many successful strategies to bypass anoikis. The main mechanism, albeit not the only one, involves hyper-activating survival pathways and over-expressing anti-apoptotic molecules. There is a strong and intertwined association between epithelial mesenchymal transition and anoikis resistance that is discussed in depth. A better understanding of anoikis resistance mechanisms has led to the research and development of pharmaceuticals that can counteract them.

Abstract: Immunotherapy (IT) and especially immune checkpoint blockade (ICB) changed the therapeutic approaches in non-small cell lung cancer (NSCLC). Still, primary or second-ary resistance and a percentage of long responders and survivors have been observed. The objective is to have a deeper understanding of the complex mechanisms of primary and secondary resistance to IT involving tumor cells, TME and host, to find strategies to over-come it. In this aim a search of the key words has been performed to identify the relevant evidence in the literature. The most available approach thus far is the combination of IT with chemotherapy (CT) and/or radiotherapy (RT), relying on the synergistic effect in enhancement of immunogenic cell death. Even so, a lot of questions are to be answered, as a dual role has been observed, considering the complex effect, especially on the TME. Preclinical and clinical studies investigate the best sequencing and timing of chemoradiation with IT, the optimal RT volumes, sites, dose/fractionation regimens, to favor immunostimulation over suppression on the TME. Moving forward, multiple agents addressing coinhibitory or costimulatory receptors, on immune or tumor cells, are under evalua-tion. In perspective, a huge potential of combination therapies is arising, but to which tar-get, to what patient, at what time and sequence to be administered, considering the complex mechanisms of resistance, needs dynamic biomarkers to guide the decisions, to-wards more personalized treatments.

Abstract: Immunotherapy has shown much promise for blood cancers, which may all be curable soon, especially if hematopoietic stem cells are harvested and frozen ahead of time for each individual. However, solid tumors are still extremely difficult to treat. For blood cancers, the entire white blood cell compartment can be eliminated and replenished by cells generated by pristine, edited hematopoietic stem cells. Obviously, solid organs cannot be eliminated in a similar fashion. Immunotherapy has still helped in some instances for solid tumors, e.g., melanoma, and may eventually be able to cure all solid tumors for reasons that are a bit unclear currently. However, I don’t think we should fully rely on that possibility – or at least wait for it if we do not have to. I have written multiple pieces about targeting truncal, i.e., clonal, mutations in cancer as a means of curing it. This would be a treatment specific to each patient. However, in my earlier work, I misunderstood the quantities of clonal mutations in most solid tumors. Although there are only a handful of clonal ‘driver’ mutations in most solid tumor patients, there are also at least a handful of clonal ‘passenger’ mutations. While traditional therapies cannot effectively target passenger mutations, directly detecting mutated transcripts allows for them to become targets.

Abstract: Background/Objectives: Advances in pediatric oncology have improved survival; however, critically ill children with cancer remain at high risk for adverse outcomes and frequently require admission to the pediatric intensive care unit (PICU). Despite the rising burden of pediatric cancer in Saudi Arabia, data on PICU utilization and outcomes are limited. This study aimed to describe the characteristics, critical care interventions, and outcomes of pediatric oncology patients admitted to a tertiary PICU and to identify predictors of mortality. Methods: A retrospective cohort study was conducted including pediatric oncology patients (< 14 years) admitted to the PICU at King Abdullah Spe-cialized Children’s Hospital, Riyadh, from 2015 to 2021. Demographic, oncologic, and clinical variables; admission indications; PRISM scores; and PICU interventions were collected. Mortality predictors were evaluated using Cox proportional hazards model-ing. Results: A total of 126 newly diagnosed pediatric oncology patients were admitted during the study period. The median age was 6 years (IQR 3–11), and 59% were female. Hematologic malignancies accounted for 63% of admissions. Sepsis (41%) and respira-tory failure (21%) were the leading indications for PICU admission. Comorbidities were present in 33% of patients, and 70% had received prior therapeutic interventions, most commonly chemotherapy. Organ dysfunction occurred in 39% of patients, including 32% with multiorgan failure. Mechanical ventilation was required in 35% of patients, inotropic support in 30%, and dialysis in a smaller proportion. The overall mortality rate was 19%, with more than half of deaths occurring during the PICU stay. Non-survivors had higher rates of comorbidities, invasive organ support, and higher PRISM scores. Mechanical ventilation (HR 3.02; 95% CI 1.16–7.60) and prior therapeutic interventions (HR 3.19; 95% CI 1.24–8.19) were independent predictors of mortality. Conclusions: Pediatric oncology patients admitted to the PICU experience substantial morbidity and mortality, underscoring the need for early risk identification and optimized supportive care.

Abstract: Introduction The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022 with little real-world data published on the topic. The aim of this study was to evaluate real world data on treatment feasibility, efficacy and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0) Results We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2%. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 1/3 of patients of the study population. pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and pCR rate (p=0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p=0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusion The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial with no treatment related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates.

Abstract: Background/Objectives: Pleural mesothelioma (PM) frequently recurs despite multimodal therapy. Here, we aimed to retrospectively evaluate the safety and potential clinical benefit of radiofrequency ablation (RFA) for recurrent PM. Methods: Fourteen consecutive patients underwent CT-guided RFA between July 2019 and June 2025. The cohort comprised 13 men and 1 woman, with a median age of 69 (range, 54–77) years. All patients had previously received systemic therapy and 12 had undergone surgery. Seven patients (50%) presented with multiple lesions, and 25 tumors (median diameter 1.8 cm; range, 0.5–7.0 cm) were treated in 23 sessions. Outcomes assessed were local tumor control, complications, and survival. Local progression and overall survival were estimated using Kaplan–Meier analysis. Adverse events were classified according to the Society of Interventional Radiology guidelines. Results: Technical success was achieved in all sessions. Two tumors showed local recurrence, corresponding to 1- and 2-year local progression rates of 10.6%. Seven patients showed distant metastases, most of whom subsequently received systemic therapy. Three patients died, two from disease progression and one from treatment-related gastrointestinal perforation during therapy for an unrelated cancer. The overall survival rates were 100%, 100%, and 60% at 1, 3, and 5 years, respectively. Major and minor complications occurred in one case each (4.3%): a refractory skin ulcer and retroperitoneal hematoma, respectively. Conclusions: RFA was technically feasible and generally well tolerated, and helped achieve encouraging local control and survival in patients with recurrent PM, warranting further evaluation of RFA as a complementary approach in multimodal treatment strategies.

Abstract: Background/Objectives: High-risk neuroblastoma (HR-NB) is a major cause of cancer-related death among children. The review aims to discuss various biochemical and genetic traits of neuroblastoma (NB) used for risk assessment and the potential of cell-based therapies for the patients with HR-NB. Methods: A comprehensive search was performed through MEDLINE, PubMed, Scopus, and ScienceDirect using various combinations of “neuroblastoma”, “tumor microenvironment (TME)”, “immune cells”, “non-immune cells”, “hematopoietic stem cell transplantation (HSCT)”, “autologous stem cell transplantation (ASCT)”, “natural killer cells (NK)”, “chimeric antigen receptor T cells (CAR-T)”, “CAR-NKT”, “tumor infiltrating lymphocytes (TIL)”, “bioinformatics”, and “neuro-antigens” in the published papers over the last decade. Reviews, systematic reviews, and clinical trials related to children’s NB were selected. The final set included 99 articles of interest. Results: Recent studies have shown that TME is crucial in determining the malignancy, immune evasion, and drug resistance of NB. Innate immune cells, including tumor associated macrophages, NK, dendritic cells, T regulatory and myeloid-derived suppressor cells or non-immune cancer-associated fibroblasts, etc. play important roles in shaping the NB TME. Depleting or reprogramming TME factors can improve the effectiveness of immunotherapy. A number of clinical trials have studied and showed feasibility of using ASCT, NK cells, CAR-T, and CAR-NKT cells in the adoptive therapy for HR-NB. Conclusion: Cell-based technologies have a high potential for the treatment of patients with HR-NB including ASCT, NKs, CAR-T, and CAR-NKT cells. Further randomized clinical trials will help determine the role of cell-based technologies in the multimodal treatment of patients with HR-NB.

Abstract: Background: Non-coding RNAs (ncRNAs) have emerged as promising biomarkers for prostate cancer (PCa), yet evidence remains dispersed across heterogeneous studies and their regulatory context is seldom analyzed in an integrated manner. This study systematically maps ncRNAs reported as diagnostic biomarkers for PCa and characterizes their molecular interactions through in silico analyses. Methods: A comprehensive evidence-mapping strategy across major bibliographic databases identified 693 studies, of which 58 met eligibility criteria. Differentially expressed ncRNAs were extracted and classified by RNA type. Subsequently, miRNA–target prediction, miRNA–protein interaction network construction, and functional enrichment analyses were performed to explore the regulatory landscape of miRNA-associated proteins. Results: The final dataset included 4,500 participants (2,871 PCa cases and 2,093 controls) and reported 94 differentially expressed miRNAs, eight lncRNAs, and several circRNAs, snoRNAs, snRNAs, and piRNAs. In silico analyses predicted 13,493 miRNA–mRNA interactions converging on 4,916 unique target genes, with an additional 2,481 prostate tissue–specific targets. The miRNA–protein network comprised 845 nodes and 2,335 edges, revealing highly connected miRNAs (e.g., hsa-miR-16-5p, hsa-miR-20a-5p) and protein hubs (QKI, YOD1, TBL1XR1; prostate-specific CDK6, ACVR2B). Enrichment analysis showed strong overrepresentation of metabolic process–related GO terms and cancer-associated KEGG pathways. Conclusions: These findings refine the list of promising ncRNA biomarkers and highlight candidates for future clinical validation.

Abstract: Background: Primary bone sarcomas (BS) are aggressive malignant tumors characterized by a high prevalence in children and adolescents and frequent lung metastasis, which significantly worsens the prognosis. Early diagnosis of recurrence and metastases after treatment is crucial for improving patient survival. Methods: This study examines exosomal microRNA as potential biomarkers for BS, which is particularly relevant in light of the development of liquid biopsy methods, which offer a noninvasive and dynamic approach to disease monitoring, early diagnosis, and evaluation of the effectiveness of anticancer therapy. Plasma exosomal microRNA levels in the plasma of patients with BS were analyzed before and after radical intraoperative thermal ablation in combination with perioperative chemotherapy using quantitative PCR. Results: The results showed that miR-92a levels were significantly different between clinically healthy donors and sarcoma patients, and after therapy, there was a tendency for the level of this microRNA to decrease in exosomes, while for miR-101, there was a tendency for the level to increase in exosomes after therapy. Conclusions: The observed relationship between microRNA levels and treatment efficacy suggests that they hold promise as noninvasive markers for the early diagnosis of relapses using liquid biopsy. Further studies involving larger patient cohorts are needed to validate the findings and determine the clinical significance of the proposed markers.

Abstract: Background: Breast cancer–related lymphedema is a frequent and disabling condition that affects function, skin quality, and psychological well-being. Early identification of tissue alterations is essential to improve management and prevent chronic fibrosis. This study aimed to develop an integrated aesthetic-medicine check-up combining clinical assessment, instrumental skin evaluation, and high-resolution ultrasound to support early diagnosis, objective stratification, and personalized cosmetological recommenda-tions. Methods: Fifteen women with unilateral upper-limb secondary lymphedema after mastectomy underwent a standardized protocol including clinical examination, palpatory assessment, skin-instrumental measurements (corneometry, sebometry, pH, transepi-dermal water loss), and high-resolution ultrasound of the dermo-epidermal complex and subcutis across 17 limb sectors. Ultrasound findings were classified into normal, fluid, sclerotic, or undifferentiated patterns and compared with clinical severity. Results: Ul-trasound detected dermal and subcutaneous alterations even in subclinical stages, re-vealing increased thickness, fluid patterns, and fibrotic changes. All patients showed reduced hydration, low superficial lipids, and increased transepidermal water loss, suggesting impairment of the skin barrier. More advanced stages were associated with sclerotic or undifferentiated ultrasound patterns, while early stages presented mostly normal or fluid profiles. The integrated evaluation enabled tailored cosmetological pre-scriptions, which improved patients’ skin comfort and supported rehabilitative strategies. Conclusions:Combining high-resolution ultrasound with dermo-aesthetic assessment enhances diagnostic accuracy and provides objective criteria for stratifying lymphedema severity. Personalized cosmetological interventions, guided by instrumental data, may support early management and contribute to improved quality of life after breast cancer treatment. This integrated model is consistent with current multidisciplinary recom-mendations and may represent a valuable addition to oncologic rehabilitation pathways.

Abstract: A disintegrin and metalloproteinase with thrombospondin motifs 6 (ADAMTS6) is an extracellular protease that promotes the invasion of lung adenocarcinoma (LUAD) cells. Herein, we investigate its role in epithelial-mesenchymal transition (EMT), a process that drives metastasis and drug resistance in LUAD. Re-analysis of microarray and RNA sequencing data from LUAD cells reveals that during EMT, TGF-β1 increases ADAMTS6 expression, presumably through the SMAD pathway, as SMAD2 loss completely blocks this effect. Moreover, it was shown that ADAMTS6 occupies hub positions within TGF-β1-associated gene networks. Using additional datasets, we found that ADAMTS6 expression increases under other EMT-inducing conditions, including IL-1β induction and acquired gefitinib resistance, but decreases upon knockdown of Twist1, a master regulator of EMT. This supports the involvement of ADAMTS6 in EMT within a broader context. Our knockout experiments in A549 cells showed that ADAMTS6 expression enhanced cell migration, invasion, colony formation, doxorubicin resistance, and expression of the mesenchymal markers N-cadherin, vimentin, and Twist1, but attenuated cell adhesion to the extracellular matrix and expression of the epithelial marker E-cadherin. Re-analysis of transcriptomic data from patient tumors demonstrates that high ADAMTS6 expression correlates with the expression of EMT markers, further supporting the ADAMTS6–EMT link. Moreover, high ADAMTS6 expression is associated with a worse survival prognosis. Overall, ADAMTS6 promotes EMT in LUAD cells and may be considered a marker of this process, as well as a potential therapeutic target for its inhibition.

Abstract: Background/Objectives: Cancer pain affects 55–95% of patients with advanced malignancy, representing a complex syndrome involving nociceptive, neuropathic, and nociplastic mechanisms. Despite therapeutic advances, two-thirds of patients with metastatic cancer experience inadequate pain control. This scoping review synthesizes recent evidence on advances in cancer pain pathophysiology and management to inform precision-based clinical approaches. Methods: Following PRISMA-ScR methodology, we searched PubMed, Embase, Scopus, and Web of Science for studies published between January 2022 and September 2025. After screening 3,412 records, 278 studies were included and analyzed across five domains: biological mechanisms, pharmacological management, interventional and neuromodulatory approaches, radiotherapy developments, and digital health innovations. Results: Recent mechanistic research reveals cancer pain arises from tumor-neuron-immune crosstalk, with malignant cells secreting neurotrophic factors that promote axonal sprouting and nociceptor sensitization. Genetic polymorphisms and epigenetic modifications contribute to inter-individual pain variability. Management strategies are evolving toward multimodal precision medicine: NSAIDs and opioids remain foundational, complemented by adjuvant agents and interventional procedures including nerve blocks, intrathecal delivery, and neuromodulation (spinal cord and dorsal root ganglion stimulation). Stereotactic body radiotherapy demonstrates superior analgesic durability versus conventional approaches. Digital health innovations, mobile applications, remote monitoring, wearables, and AI-enabled predictive models, enable continuous assessment and personalized treatment optimization. Conclusions: Cancer pain management is transitioning toward mechanism-based precision medicine integrating biological insights, advanced interventional techniques, and digital technologies. However, implementation challenges persist, including limited randomized trials for interventional approaches, incomplete external validation of AI tools, and digital health equity concerns. Future research must prioritize prospective controlled studies and equitable integration into routine care.

Abstract:

Background: This study explores the therapeutic potential of radiodynamic therapy (RDT), a combination of the photosensitizer 5-aminolevulinic acid (5-ALA) administration and X-ray irradiation, for high-grade glioma (HGG). The research aims to verify the RDT efficacy in both normoxic and hypoxic environments, examine its mechanisms, and assess its impact on the tumor micro-immune environment to address resistance to RDT. Methods: Glioma cell lines U87MG and U251MG were used in experiments in vitro. The cells were divided into four groups with or without 5-ALA and X-ray exposure. Results: Results demonstrated that RDT was effective under normoxia (20% O2), increasing reactive oxygen species (ROS) production and significantly decreasing U87MG cell viability in a 5-ALA concentration-dependent manner at 2Gy and 6Gy. However, under hypoxic conditions (3% O2) or long-term 3% O2 exposure, the RDT effect was not significant compared to controls. The study also found that RDT under normoxia influenced immune reaction-related gene expression, while under hypoxia, it primarily affects genes related to epithelial-mesenchymal transition (EMT). Further analysis revealed that RDT reduces the secretion of soluble PD-L1, a marker of immune checkpoint inhibition, in a 20% O2 environment. Additionally, RDT suppressed the vascular endothelial growth factor (VEGF), an angiogenesis marker, under 3% O2 conditions. RDT also reduced the secretion of colony-stimulating factor -1 (CSF-1), a differentiation inhibitory marker for macrophages, in a 20% O2 environment. Conclusion: In conclusion, this study provides evidence that RDT, combining 5-ALA and X-ray irradiation, has potential as a therapeutic strategy for HGG, especially under normoxic conditions. It may also offer benefits under hypoxia, particularly in inhibiting angiogenesis. The study also highlights the importance of understanding the role of oxygen levels in the efficacy of RDT and its potential impact on immune responses, angiogenesis, and macrophage differentiation in the tumor microenvironment. Further research is needed to fully elucidate the underlying mechanisms and optimize RDT for clinical application.

Abstract:

Cell-based drug delivery has emerged as a powerful strategy to improve therapeutic targeting while reducing systemic toxicity. This approach is particularly valuable for anticancer agents, which are often limited by severe side effects arising from off-target activity and non-specific distribution. By using cells as carriers, drugs can evade immune clearance, achieve prolonged circulation, and improve pharmacokinetic profiles, ultimately enhancing therapeutic efficacy. This review surveys the current landscape of cell-mediated drug delivery in oncology, emphasizing both fundamental principles and practical applications. We discuss the design and preparation of cellular carriers, examine the unique characteristics of commonly used cell types, and highlight recent technological innovations that are expanding their theranostic potential, focusing on strategies for delivery to challenging anatomical sites, with a dedicated focus on the brain. By consolidating recent advances and insights, this review aims to provide a comprehensive perspective on the promise and future directions of cell-based drug delivery for cancer therapy.

Abstract: Fibroblast growth factor 12 (FGF12), a member of the intracellular fibroblast growth factor homologous factor (FHF) subfamily, has been widely studied for its role in the modulation of voltage-gated ion channels. However, recent studies suggest that FGF12 possesses various cellular function beyond ion channel regulation, particularly in cancer progression. Accumulating evidence indicates that the upregulation of FGF12 is associated with tumor survival, therapeutic resistance, and poor prognosis through signaling pathways independent of its canonical ion channel interactions. This review summarizes the current understanding of FGF12’s non-canonical functions, highlights its emerging roles in cellular regulation, and discusses its potential mechanism in oncogenic progression. Understanding these novel functions may provide a new aspect for therapeutic targeting of FGF12 in malignancies.

Abstract: Cervical cancer remains a major global health burden, disproportionately affecting women in low- and middle-income countries despite being largely preventable. Since 2018, rapid advances in molecular profiling, immunotherapy, minimally invasive surgery refinement, and targeted therapeutics have transformed diagnostic and therapeutic paradigms. This narrative review synthesizes clinical and translational progress across the continuum of care from 2018 to 2025. We summarize the evolving landscape of precision screening—including HPV genotyping, DNA methylation assays, liquid biopsy, and AI-assisted cytology—and discuss their implications for global elimination goals. Surgical management has shifted toward evidence-based de-escalation with data from SHAPE, ConCerv, and ongoing RACC informing fertility preservation and minimally invasive approaches. For locally advanced disease, KEYNOTE-A18 establishes pembrolizumab plus chemoradiation as a new curative standard, while INTERLACE underscores the benefit of induction chemotherapy. In the metastatic setting, survival outcomes have improved with the integration of checkpoint inhibitors (KEYNOTE-826, BEATcc, EMPOWER-Cervical 1), vascular-targeted therapies, and antibody–drug conjugates, including tisotumab vedotin and emerging HER2 and TROP-2–directed agents. We further highlight emerging biomarkers—PD-L1, TMB, MSI status, HPV integration patterns, APOBEC signatures, methylation classifiers, ctHPV-DNA—and their evolving role in treatment selection and surveillance. Future directions include neoadjuvant checkpoint inhibition, PARP-IO combinations, HER3-directed ADCs, DDR-targeted radiosensitizers, HPV-specific cellular therapies, and AI-integrated precision medicine. Collectively, these advances are reshaping cervical cancer care toward biologically individualized, globally implementable strategies capable of accelerating WHO elimination targets.

Abstract:

Colorectal carcinoma (CRC) exerts a growing global disease burden, with microsatellite-stable/proficient mismatch repair (MSS/pMMR) tumors exhibiting intrinsic refractoriness to immune-checkpoint blockade (ICB) owing to low tumor mutational burden, limited neoantigenicity, and an immunosuppressive tumor microenvironment (TME) dominated by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This review evaluates induced pluripotent stem cell (iPSC)–derived polyvalent vaccines as ontogenetically recapitulative immunogens capable of reinstating broad antitumor immunity. Reprogramming induces re-expression of oncofetal tumor-associated antigens, including cancer-testis antigens (NY-ESO-1, MAGE-A3), aberrant glycoforms of CEA and MUC1, and clinically actionable neoepitopes such as KRAS^G12D/V, thereby promoting epitope spreading and immunogenic cell death. Irradiated autologous or syngeneic iPSCs, delivered with Toll-like receptor 9 agonists, facilitate robust MHC I/II cross-presentation, driving CD8⁺ cytotoxic T-cell activation, Th1 polarization, perforin/granzyme-mediated cytolysis, and favorable effector-to-suppressor ratios. Preclinical models of melanoma, pancreatic ductal adenocarcinoma, and MSS CRC demonstrate prophylactic and therapeutic efficacy, with neoantigen-enhanced iPSCs synergizing with radiotherapy-induced DAMPs to achieve durable regressions and memory T-cell formation. Translational priorities include CRISPR-engineered hypoimmunogenic iPSC platforms, GMP-compatible non-integrating reprogramming, and combinatorial integration with STING agonists, ICB, CAR-NK cells, and LNP-mRNA constructs to enable biomarker-guided clinical deployment in minimal-residual-disease CRC.