Cancer Therapy Research Articles

ARL6IP5 in cancers: bidirectional function and therapeutic value.

ARL6IP5 (ADP-ribosylation-like factor 6 interacting protein 5) plays an important role in a variety of physiological or pathological processes, including in cancers. However, the biological roles of ARL6IP5 in cancers are controversial. In this mini-review, we summarized the current understanding on the role of ARL6IP5 in cancers, particularly in the progression of chronic hepatitis virus-related hepatocellular carcinoma, as well as the potential values of ARL6IP5 in cancer therapy.

Metabolomic Associations With Fatigue and Physical Function in Children With Cancer: A Pilot Study.

Background: Fatigue is a frequently reported symptom in children undergoing cancer treatment. Prior research shows an inverse relationship between fatigue and physical activity. Less is known about fatigue's relationship with physical function or the underlying biological mechanisms of fatigue. This study explored associations among fatigue, physical function, and associated metabolites. Methods: Children (7-18 years) provided serum samples and self-reports of fatigue and lower extremity physical function (mobility) using Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) surveys at two timepoints during cancer therapy. PROMIS scores were categorized as high/low per established cut points (high fatigue T >47.5; high physical function T >51.5). High-resolution liquid chromatography-mass spectrometry extracted 29 metabolites hypothesized a priori to be associated with fatigue or physical function. Descriptive statistics summarized PROMIS scores, and linear mixed effect models estimated metabolite associations adjusting for age, gender and steroid use. Results: Forty children participated (female, 53%; 7-12 years, 38%; 13-18 years 62%; Hodgkins Lymphoma, 33%; Acute Lymphoblastic/Lymphocytic Leukemia, 40%; Osteosarcoma, 10%; Other, 17%). Physical function and fatigue were inversely related: T1 (r = -0.64; p < .001) and T2 (r = -0.63; p < .001). One metabolite (indole-3-latic acid) differentiated between low and high fatigue. Five metabolites differentiated significantly between low and high physical function (4-Hydroxybenzoic acid, m-Coumaric acid, myoinositol, tryptophan, and tyrosine). Conclusions:These findings substantiate prior studies showing metabolites, particularly amino acids, significantly associated with fatigue and physical function. All significant metabolites were associated with the gut microbiome. Physical function was inversely corelated with fatigue providing another potential intervention for fatigue management.

MRI-Guided Adaptive Radiation Therapy for Oligometastatic Prostate Cancer Involving the Adrenal Gland: A Case Report and Literature Review

MRI-Guided Adaptive Radiation Therapy for Oligometastatic Prostate Cancer Involving the Adrenal Gland: A Case Report and Literature Review

Unveiling the BRAF fusion structure variations through DNA and RNA sequencing.

The detection of BRAF fusions by using next-generation sequencing (NGS) is essential for comprehensive analysis. Data BRAF positive rearrangements from Chinese cancer patients were analyzed. DNA NGS was performed on FFPE samples, and RNA NGS was used to confirm fusion transcripts. BRAF fusions were identified in various cancers, predominantly glioma (87.8%). DNA NGS detected 371 BRAF fusion-positive samples, with 338 retaining the serine/threonine receptor tyrosine kinase domain (RTKD), divided into four groups: common (n = 254), rare (n = 66), intergenic (n = 7), and exonic (n = 11) fusions. Common fusions, mainly KIAA1549-BRAF, comprised the majority, with variations at introns 8, 9, and 10. Rare fusions and intergenic/exonic breakpoints displayed diverse structural patterns. RNA NGS verified transcriptional consistency in most samples from common fusions. However, various outcomes at the RNA level were found in other groups, involving mechanisms like alternative splicing, antisense rearrangement, and frameshift rearrangement. Additionally, 33 fusions lacked the RTKD, demonstrating significant structural diversity. Furthermore, 22 novel fusions were identified, which were distributed in tongue cancer, liver cancer, lung cancer, melanoma, brain cancer, and colon cancer. Comprehensive molecular profiling and RNA sequencing are essential for accurate fusion detection, improving the design of NGS panels and aiding in the targeted therapy of BRAF fusion-positive cancers.

Perioperative complications of focal therapy for prostate cancer: results from the GeRmAn Nationwide inpatient Data (GRAND) study.

To compare the perioperative complications of the most common focal therapy (FT) modalities for prostate cancer. We assessed the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2023, provided by the Research Data Center of the Federal Bureau of Statistics. We compared perioperative outcomes of high-intensity focused ultrasound (HIFU), hyperthermia, irreversible electroporation of the prostate, cryotherapy, vascular photodynamic therapy of the prostate (VTP), and transurethral ultrasound ablation, as well as HIFU vs non-HIFU treatments in general. Furthermore, we evaluated the role of concomitant transurethral resection of the prostate (TURP) on perioperative complications. Finally, the complication rate of FT was also compared to brachytherapy and robot-assisted radical prostatectomy. A total of 10 544 underwent FT. Most patients received HIFU (92%). The number of FT cases performed annually has been steadily decreasing. The most prevalent complication (9.6%) was urinary tract infection (HIFU: 10%, hyperthermia: 6.2%, cryotherapy: 6.8%, VTP: 3.9%). Haematuria was observed in 3.6% of all cases. In the multivariable regression, HIFU was associated with higher rates of urinary tract infections (10% vs 5.2%, P < 0.001) but lower rates of haematuria (3.4% vs 5.5%, P < 0.001) and admission to the intensive care unit (0.7% vs 2.2%, P < 0.001) compared to non-HIFU procedures. Concomitant TURP was associated with higher transfusion (P < 0.001), haematuria (P < 0.001), sepsis (P = 0.001), and urinary retention rates (P = 0.03). Most perioperative complications were statistically significantly worse in patients undergoing FT compared to brachytherapy, while most perioperative complications were better after FT vs robot-assisted radical prostatectomy. In the largest epidemiological comparative study on the risk of complications of the most common FT for prostate cancer, we were able to show an overall low risk of perioperative complications.

Engineering Folic Acid-Modified Nanoparticles to Enhance Letrozole's Anticancer Action.

The development of biodegradable nanoparticles (NPs) for delivering anticancer drugs, such as letrozole (LTZ), offers a targeted approach for cancer therapy. In this study, we synthesized poly(ε-caprolactone)-co-poly(ethylene glycol) (PCL-co-PEG) and fabricated LTZ-loaded PCL-co-PEG NPs (LTZ-NPs) via emulsion-solvent evaporation. Folic acid (FA), a folate receptor-targeting molecule, was conjugated to the LTZ-loaded NPs (LTZ-FNPs) to enhance treatment efficacy against hormone receptor-positive breast cancer cells. Both NPs and FNPs exhibited a spherical morphology (60-90 nm), with FNPs showing higher drug entrapment efficiency and controlled release. LTZ release was minimal at physiological pH but increased in acidic, cancer-like environments, following the Korsmeyer-Peppas model, indicating a combination of Fickian and non-Fickian diffusion. In cytotoxicity assays, LTZ-FNPs exhibited higher toxicity against MCF-7 cells than LTZ-NPs. Controlled LTZ release altered gene expression, reducing B-cell leukemia/lymphoma 2 protein (Bcl2) and increasing caspase 8 (Casp8), promoting apoptosis. A shift to the SubG1 phase further confirmed enhanced LTZ-FNP-mediated cell death. Furthermore, p53 expression increased, while matrix metalloproteinase 9 (MMP-9) decreased, inhibiting cell invasion. This study introduces a biodegradable system with FA-functionalized, pH-sensitive NPs for the targeted and controlled delivery of LTZ. This approach holds great potential for selective, efficient treatment while minimizing systemic toxicity in breast cancer therapy.

Oncological needs in transgender patients.

Transgender people encounter unique health disparities in oncology. They face substantial barriers in accessing healthcare that are exaggerated by bias/discrimination from healthcare professionals and systems, and socio-economic marginalisation. This review explores the current landscape of cancer risk, screening and management in transgender individuals from a Spanish perspective. Nationwide data are lacking, but estimates from Madrid suggest that 22 per 100,000 individuals are transgender. The needs of the transgender individual for gender-affirming surgeries and gender-affirming hormone therapy may alter the individual's oncological risk profile and likelihood of receiving appropriate screening, and when diagnosed with cancer may have to be balanced against treatment requirements (e.g., endocrine therapy for breast cancer). There remain unmet needs in the oncological care of the transgender patient. Concerted effort is required to address clinical research gaps, and reform healthcare education and policy, in order to develop inclusive clinical practices that enhance patient care and outcomes.

HEX-1 reduces colitis-driven colorectal cancer via inactivating the prolyl isomerase PIN1 sensitization and remodeling the gut microbiota

Metabolic reprogramming, a pivotal hallmark of cancer, plays a crucial role in both the initiation and progression of colorectal cancer (CRC). Despite the vast unknowns surrounding the identity and biological activities of most natural metabolites in diseases, our study, utilizing native metabolomics results through GC–MS/MS, identified a small molecule, 4,4-Dimethyl-2-cyclohexen-1-one, named HEX-1 in the serum of CRC patients. We have further explored and assessed its biological activities. HEX-1 suppressed the proliferation of cancer cells and tumorigenesis via the inactivation and sensitization of PIN1. Notably, HEX-1 exhibits similar functional effects as all-trans retinoic acid (atRA) but stands out by not inducing the degradation of PIN1 mRNA or protein expression, unlike biological compounds associated with atRA. HEX-1 demonstrated the ability to induce G1/S arrest in vitro and ameliorate the progression of inflammatory CRC in mice by remodeling the gut microbiota. As volatile organic compounds (VOCs), HEX-1 could be detected feasibly. Its unique ability to penetrate whole cell populations positions it as a promising approach for cancer therapy and as an enhancer for chemotherapy and immunotherapy. The findings suggest that HEX-1 holds the potential as a valuable addition to the armamentarium against CRC.Graphical

The effects of ozone exposure on apoptotic mechanisms in Colo-320 and Colo-741 cell lines: implications for cancer therapy.

This study aimed to investigate the effects of ozone exposure on apoptotic mechanisms in primary (Colo-320) and metastatic (Colo-741) cell lines. Colo-320 and Colo-741 cells were grown in RPMI-1640 medium supplemented with 10% fetal bovine serum and treated with 20µg/mL ozone for 72h after MTT assay. Inverted microscopy was used for morphological assessment, and immunocytochemistry followed by H-SCORE analysis was performed to measure the expression of apoptotic markers. The statistical analysis was conducted using unpaired T-tests or Mann-Whitney U tests, with significance set at p < 0.05. Morphological analysis showed no significant changes in cell shape in Colo-320 or Colo-741 cells after ozone exposure. However, immunocytochemical analysis revealed significant increases in semi-quantitative histological scores (H-SCORES) for cleaved caspase-3, Bax, and cytochrome c in both cell lines, indicating enhanced apoptotic activity (p < 0.05). Conversely, Bcl-2 expression was significantly decreased in both Colo-320 and Colo-741 cell lines after ozone exposure (p < 0.05). Ozone exposure promoted apoptosis in both Colo-320 and Colo-741 cell lines, as evidenced by increased pro-apoptotic markers and decreased anti-apoptotic markers. These molecular changes were notable, yet they did not visibly alter cell morphology. The observed similarities between Colo-320 and Colo-741 cell responses suggest the need for further investigation. These findings indicate that ozone exposure may influence tumor cell apoptosis while preserving cell structure, highlighting the necessity of further research into its potential therapeutic implications.

Multifunctional and Scalable Nanoparticles for Bimodal Image-Guided Phototherapy in Bladder Cancer Treatment

Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine. Here, we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles (PPBC LNPs) as a bimodal system for image-guided phototherapy in bladder cancer treatment. PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation, but also exhibit potent autophagy blockage, effectively inducing bladder cancer cell death. Furthermore, PPBC LNPs possess remarkable photoacoustic (PA) and fluorescence (FL) imaging capabilities, enabling imaging with high-resolution, deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy. Specifically, PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy, while FL imaging confirms their prolonged retention at the tumor site for up to 6days. PPBC LNPs significantly suppress bladder tumor growth, with several tumors completely ablated following just two doses of the nanoparticles and laser treatment. Additionally, PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility, stability, and scalability, showing potential for clinical translation. This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.

RBCs as a Bioinspired Drug Delivery System for Co-delivery of Irinotecan and Nanoalumina Enhances Colorectal Cancer Therapy.

Colorectal cancer (CRC) is a malignant epithelial tumor with high morbidity and mortality. In CRC treatment, irinotecan (CPT-11) as a chemotherapeutic drug is widely applied. However, its half-life is short, leading to large dosages and severe side effects. Red blood cells (RBCs) are biocompatible drug carriers with high capacity, avoiding premature drug degradation and achieving slow drug release. Nanoalumina (AN) is an emerging immune adjuvant that can enhance the immune response. Here, we used RBCs as carriers and absorbed AN to construct AN-CPT-11-RBCs. CPT-11 would induce tumor cell death, releasing much tumor antigen, while AN would activate immune cells to recognize newly released antigens and induce lymphocyte proliferation, enhancing the antitumor effect simultaneously. With loading amounts of 4 mg of CPT-11 and 3 mg of AN per 109 RBCs, AN-CPT-11-RBCs had similar properties to natural RBCs. In vivo, AN-CPT-11-RBCs could circulate for 9 days and stimulate the proliferation of lymphocytes in the spleen and tumor tissue, having a higher tumor growth inhibition rate of 74.01% and a lower frequency of administration. In conclusion, AN-CPT-11-RBCs attain the co-delivery of CPT-11 and AN for the synergistic treatment of CRC.

Single-cell RNA sequencing of human double-negative T cells reveals a favorable cellular signature for cancer therapy

BackgroundAllogeneic double-negative T-cell (DNT) therapy has emerged as a novel, off-the-shelf cellular treatment with clinical feasibility, safety, and promising efficacy against leukemia. However, the biology of DNTs is less well...

Engineering Magnetotactic Bacteria as Medical Microrobots.

Nature's ability to create complex and functionalized organisms has long inspired engineers and scientists to develop increasingly advanced machines. Magnetotactic bacteria (MTB), a group of Gram-negative prokaryotes that biomineralize iron and thrive in aquatic environments, have garnered significant attention from the bioengineering community. These bacteria possess chains of magnetic nanocrystals known as magnetosomes, which allow them to align with Earth's geomagnetic field and navigate through aquatic environments via magnetotaxis, enabling localization to areas rich in nutrients and optimal oxygen concentration. Their built-in magnetic components, along with their intrinsic and/or modified biological functions, make them one of the most promising platforms for future medical microrobots. Leveraging an externally applied magnetic field, the motion of MTBs can be precisely controlled, rendering them suitable for use as a new type of biohybrid microrobotics with great promise in medicine for bioimaging, drug delivery, cancer therapy, antimicrobial treatment, and detoxification. This mini-review provides an up-to-date overview of recent advancements in MTB microrobots, delineates the interaction between MTB microrobots and magnetic fields, elucidates propulsion mechanisms and motion control, and reports state-of-the-art strategies for modifying and functionalizing MTB for medical applications.

Ultrafast Laser-Induced 1T'/2H-MoTe2 Nanopattern with Au-Nanoclusters for Raman Monitoring of Cellular Drug Metabolism.

The development of surface-enhanced Raman spectroscopy (SERS) as an ultrasensitive fingerprint analysis technique in precision medicine requires high-performance SERS substrates with controllable nanostructure (hot-spot) distribution, simple fabrication, superior stability, biocompatibility, and extraordinary optical responses. Unfortunately, fabrication of arbitrary nanostructures with high homogeneity on a large scale for SERS is still challenging. Herein, we report an ultrafast laser parallel fabrication protocol for Au/2D-transition-metal dichalcogenide hybrid SERS biosensors. The leveraged photonic nanojets (PNJs) are generated by a micron-sized microsphere monolayer to simultaneously trigger localized phase transition in 2H-MoTe2, achieving a 1T'-MoTe2 nanopattern array with a density of 1 million per mm2 by a single laser shot. The Au nanoparticle clusters (AuNCs) are subsequently grown in situ from the 1T' regions, creating a AuNCs on 1T'/2H-MoTe2 (AuNCs@1T'/2H-MoTe2) hybrid SERS substrate. The fabricated feature diameter and overlay accuracy of the patterned AuNCs are 210.1 ± 3.4 and 9.2 ± 1.7 nm, respectively. To eliminate background noise, we designed dimer-AuNCs@1T'/2H-MoTe2 (dAuNCs@1T'/2H-MoTe2), achieving a detection limit of 10-13 M with an enhancement factor of 4.9 × 108 for the methylene blue (MB) analyte. The strong localized surface plasmon resonances in the dAuNCs as well as efficient charge transfers between Au, 2H-MoTe2, and MB contribute to the majority of Raman enhancement. The multiscale dAuNCs@1T'/2H-MoTe2 array provides a powerful SERSome (comprising multiple SERS spectra) platform for therapeutic drug monitoring, by which we successfully identified the metabolic behaviors of living gastric adenocarcinoma cells administered with two drugs, i.e., capecitabine, oxaliplatin, and their combination. The present work establishes opportunities for creating a highly ordered nanopattern array for ultrasensitive SERSome analysis of cell metabolism in cancer therapy.

TRIM25 facilitates ferroptosis in ovarian cancer through promoting PIEZO1 K63-linked ubiquitination and degradation.

TRIM25 facilitates ferroptosis in ovarian cancer through promoting PIEZO1 K63-linked ubiquitination and degradation.

Targeting breast cancer: the promise of phage-based nanomedicines.

Breast cancer is a leading cause of cancer-related mortality among women worldwide, characterized by its aggressive nature, propensity for metastasis, and resistance to standard treatment modalities. Traditional therapies, including surgery, chemotherapy, and radiation, often encounter significant limitations such as systemic toxicity and lack of specificity. This review aims to evaluate the recent advancements in phage-based nanomedicines as a novel approach for targeted breast cancer therapy, focusing on their mechanisms of action, therapeutic benefits, and the challenges faced in clinical implementation. A comprehensive literature review was conducted, analyzing studies that investigate the application of bacteriophages in cancer therapy, particularly in breast cancer. The review highlights the integration of nanotechnology with phage therapy, examining the potential for enhanced targeting and reduced side effects. Phage-based nanomedicines have shown promise in selectively targeting breast cancer cells while sparing healthy tissues, thereby improving therapeutic efficacy and safety profiles. The unique properties of bacteriophages, including their ability to be engineered for specific targeting and their natural ability to induce immune responses, present significant advantages over conventional treatments. The integration of phage therapy with nanotechnology represents a promising frontier in the fight against breast cancer. This review underscores the need for continued research to address existing challenges and to explore the full potential of phage-based nanomedicines in improving patient outcomes in breast cancer treatment.

Combinatorial CRISPR screen reveals FYN and KDM4 as targets for synergistic drug combination for treating triple negative breast cancer.

Tyrosine kinases play a crucial role in cell proliferation and survival and are extensively investigated as targets for cancer treatment. However, the efficacy of most tyrosine kinase inhibitors (TKIs) in cancer therapy is limited due to resistance. In this study, we identify a synergistic combination therapy involving TKIs for the treatment of triple negative breast cancer. By employing pairwise tyrosine kinase knockout CRISPR screens, we identify FYN and KDM4 as critical targets whose inhibition enhances the effectiveness of TKIs, such as NVP-ADW742 (IGF-1R inhibitor), gefitinib (EGFR inhibitor), and imatinib (ABL inhibitor) both in vitro and in vivo. Mechanistically, treatment with TKIs upregulates the transcription of KDM4, which in turn demethylates H3K9me3 at FYN enhancer for FYN transcription. This compensatory activation of FYN and KDM4 contributes to the resistance against TKIs. FYN expression is associated with therapy resistance and persistence by demonstrating its upregulation in various experimental models of drug-tolerant persisters and residual disease following targeted therapy, chemotherapy, and radiotherapy. Collectively, our study provides novel targets and mechanistic insights that can guide the development of effective combinatorial targeted therapies, thus maximizing the therapeutic benefits of TKIs.

The G protein-coupled receptor GPR89A is a novel potential therapeutic target to overcome cisplatin resistance in NSCLC Calu1 cells.

Lung cancer is the most frequently diagnosed cancer type worldwide and is characterised by its high metastatic potential. Standard therapy for nonsmall cell lung cancer (NSCLC) cases includes chemotherapy with the platinum-based chemotherapeutic agent cisplatin. Although lung cancer cases respond well to cisplatin at the beginning of treatment, ~ 60% develop chemotherapy resistance during this process. In this study, a genome-wide CRISPR-Cas9-based genetic screening approach was employed to identify genes that cisplatin-resistant NSCLC Calu1 cells are more addicted to than sensitive cells. Cisplatin-resistant Calu1 cells were generated by the dose escalation method, and genome-wide CRISPR-Cas9-based genetic screening was performed with the Brunello CRISPR knockout library. Bioinformatics analyses of the obtained next-generation sequencing data revealed 63 potential candidate genes responsible for cisplatin resistance, including G protein-coupled receptor 89A (GPR89A), Poly(U) binding splicing factor 60 (PUF60), NBAS subunit of NRZ tethering complex (NBAS) and GrpE like 1, mitochondrial (GRPEL1). The GPR89A protein is located in the Golgi cisterna and Golgi-associated vesicle membrane, enables voltage-gated anion channel activity, and is involved in intracellular pH reduction. Functional studies carried out with GPR89A-knockout cisplatin-resistant Calu1 cells resulted in cell cycle arrest in the G2/M phase and increased polyploidy, and also prevented colony formation and cell migration. Cisplatin treatment, on the other hand, resulted in increased cell death by apoptosis upon cell cycle arrest in the S phase. In conclusion, this is the first study that identified GPR89A as a potential therapeutic target to overcome cisplatin resistance in NSCLC Calu1 cells.

Porphyrin-Derived Carbon Dots for Red-Light Activated Photodynamic Therapy of Breast Cancer.

In recent years, cancer has emerged as a major global health threat, ranking among the top causes of mortality. While treatments such as surgery, immunotherapy, radiation therapy, and chemotherapy remain widely used, photodynamic therapy has been gaining significant interest. Most of the photosensitizing agents employed in clinical settings are derived from tetrapyrrolic frameworks, including porphyrins, chlorins, and phthalocyanines. Although these compounds have demonstrated therapeutic effectiveness, they suffer from critical drawbacks, such as limited solubility in water and inadequate (photo)stability. To address these issues, herein, the formulation of the previously reported and promising photosensitizer tetrakis(4-carboxyphenyl) porphyrin into carbon dots is reported. The carbon dots were found with enhanced aqueous solubility, high (photo)stability, and greater singlet oxygen quantum yield overcoming the limitations of the molecular photosensitizer. While being nontoxic in the dark, the carbon dots induced a phototherapeutic effect in breast cancer cells and multicellular tumor spheroids.

Evaluation of Nectin-4 and Trop-2: implications for patient outcomes and therapy in penile cancer.

Evaluation of Nectin-4 and Trop-2: implications for patient outcomes and therapy in penile cancer.