A growing number of peer-reviewed publications have reported diverse cancer types appearing in temporal association with COVID-19 vaccination or infection. To characterize the nature and scope of these reports, a systema...A growing number of peer-reviewed publications have reported diverse cancer types appearing in temporal association with COVID-19 vaccination or infection. To characterize the nature and scope of these reports, a systematic literature search from January 2020 to October 2025 was conducted based on specified eligibility criteria. A total of 69 publications met inclusion criteria: 66 article-level reports describing 333 patients across 27 countries, 2 retrospective population-level investigations (Italy: ~300,000 cohort, and Korea: ~8.4 million cohort) quantified cancer incidence and mortality trends among vaccinated populations, and one longitudinal analysis of ~1.3 million US miliary service members spanning the pre-pandemic through post-pandemic periods. Most of the studies documented hematologic malignancies (non-Hodgkin's lymphomas, cutaneous lymphomas, leukemias), solid tumors (breast, lung, melanoma, sarcoma, pancreatic cancer, and glioblastoma), and virus-associated cancers (Kaposi and Merkel cell carcinoma). Across reports, several recurrent themes emerged: (1) unusually rapid progression, recurrence, or reactivation of preexisting indolent or controlled disease, (2) atypical or localized histopathologic findings, including involvement of vaccine injection sites or regional lymph nodes, and (3) proposed immunologic links between acute infection or vaccination and tumor dormancy, immune escape, or microenvironmental shifts. The predominance of case-level observations and early population-level data demonstrates an early phase of potential safety-signal detection. These findings underscore the need for rigorous epidemiologic, longitudinal, clinical, histopathological, forensic, and mechanistic studies to assess whether and under what conditions COVID-19 vaccination or infection may be linked with cancer.
Human Papilloma Virus (HPV) is a causative agent in several cancers including cervical cancer, head and neck cancer, anal cancer, penile, vulvar and vaginal cancers. HPV through its virus-encoded protein E6 and the cellu...Human Papilloma Virus (HPV) is a causative agent in several cancers including cervical cancer, head and neck cancer, anal cancer, penile, vulvar and vaginal cancers. HPV through its virus-encoded protein E6 and the cellular E6-Associated Protein (E6-AP) target the tumor suppressor p53 protein for degradation thereby contributing to cancer development after HPV infection. As viruses cause cancer, the author previously hypothesized that SARS-COV-2 virus may be associated with cancer. More recent insights on the present hypothesis have come from studies suggesting (1) Spike protein of SARS-COV-2 may suppress p53 function, (2) cancer has been associated with mRNA vaccines that produce Spike, and (3) a case mentioned by Dr. Patrick Soon Shiong of a patient who survived HPV-associated head and neck cancer, but the tumor recurred after COVID mRNA vaccination including with liver metastases. Thus, the present hypothesis is that virally encoded proteins such as HPV-E6 or SARS-COV-2 Spike may cooperate in suppressing host defenses including tumor suppressor mechanisms involving p53. The hypothesis can be further explored through epidemiologic and laboratory studies.
BACKGROUND/OBJECTIVES: Mutant KRAS (mtKRAS) tumors are highly immunosuppressive, largely through secretion of IL-10 and TGF-β2, which prevent immune cell infiltration. Nerofe (dTCApFs), a peptide derivative of Tumor Cell...BACKGROUND/OBJECTIVES: Mutant KRAS (mtKRAS) tumors are highly immunosuppressive, largely through secretion of IL-10 and TGF-β2, which prevent immune cell infiltration. Nerofe (dTCApFs), a peptide derivative of Tumor Cell Apoptosis Factor, induces endoplasmic reticulum stress and modulates immune signaling through the T1/ST2 receptor, which is overexpressed in mtKRAS tumors. We evaluated whether combining Nerofe with low-dose doxorubicin (ldDox) could remodel the immune microenvironment and overcome tumor immunosuppression. METHODS: experiments were performed in PANC-1 pancreatic adenocarcinoma cells harboring a KRAS mutation. Cytokine expression, c-Jun activity, and c-Jun-ST2 binding were measured by western blotting, immunocytochemistry, and immunoprecipitation. In a clinical trial (NCT05661201), patients with mtKRAS tumors received weekly Nerofe (288 mg/m²) plus ldDox (8 mg/m²). Tumor biopsies were analyzed by immunohistochemistry before treatment and after 7 weeks. RESULTS: Nerofe+ldDox treatment increased IL-2 and suppressed IL-10 in PANC-1 cells, reversing the immunosuppressive cytokine profile. Patient biopsies confirmed these effects, showing higher IL-2, lower IL-10, and increased infiltration of NK cells, CD8 cytotoxic T lymphocytes, and CD4 helper T cells. KRAS protein levels were reduced in post-treatment biopsies. Mechanistically, Nerofe+ldDox elevated total c-Jun protein but reduced phosphorylation at Ser63 and Ser73. Co-immunoprecipitation showed that c-Jun was bound to nuclear ST2 under basal conditions; this complex was disrupted within 3 h of treatment, releasing c-Jun to activate IL-2 and miR-217 transcription before re-forming after 24 h. This transient release corresponds to the early induction of IL-2 and later reduction in KRAS levels. CONCLUSIONS: Nerofe+ldDox reprograms the immune microenvironment of mtKRAS tumors by releasing c-Jun from inhibitory nuclear ST2, enabling expression of IL-2 and miR-217. This "nuclear immunomodulation" promotes immune cell infiltration and downregulates KRAS expression, highlighting Nerofe+ldDox as a promising therapeutic approach for mtKRAS-driven cancers.
Colorectal cancer (CRC) is one of the most common and lethal types of cancer worldwide. Understanding both the biological and clinical aspects of the patient is essential to uncover the mechanism underlying the prognosis...Colorectal cancer (CRC) is one of the most common and lethal types of cancer worldwide. Understanding both the biological and clinical aspects of the patient is essential to uncover the mechanism underlying the prognosis of the disease. However, most current approaches focus primarily on clinical or biological elements, which can limit their ability to capture the full complexity of the prognosis of CRC. This study aims to enhance understanding of the mechanisms of CRC by combining clinical and biological data from CRC patients with machine learning techniques (ML) to explore the importance of features and predict patient survival. First, we performed differential expression analysis and inspected patient survival curves to identify relevant biological features. Then, we applied ML techniques to understand the individual impact of each clinical and biological feature on patient survival. , , and stood out as biological features, while pathological stage, age, new tumor event, lymph node count, and chemotherapy have shown themselves as interesting clinical features. Furthermore, our ML model achieved an accuracy of 89.58% to predict patient survival. The clinical and biological features proposed here in conjunction with ML can improve the interpretation of CRC mechanisms and predict patient survival.
Key objective: To illustrate the first-hand journey of three early phase trial participants highlighting their benefits and challenges of participation and patient-centric innovations required to improve trial experience...Key objective: To illustrate the first-hand journey of three early phase trial participants highlighting their benefits and challenges of participation and patient-centric innovations required to improve trial experience. Knowledge generated: Early phase trials have traditionally centred on dose-finding and toxicity. However as they have increased in number and improved in therapeutic intent, the patient experience becomes increasingly important. This article illustrates benefits of participation including access to novel therapies, support and close monitoring but challenges around eligibility criteria, finances, and communication. Proposed solutions including trial navigators, enhanced communication training, and greater flexibility in enrolment criteria to improve trials access.
has captured major attention recently because of its health benefits and extensive research highlighting its potential in cancer treatment and prevention. Evidence suggests that can actively fight against various types...has captured major attention recently because of its health benefits and extensive research highlighting its potential in cancer treatment and prevention. Evidence suggests that can actively fight against various types of cancer, including those of the colon, lungs, breast, and stomach. Research indicates that several species of can potentiate the action of chemotherapy, immunotherapy and radiation therapy in battling tumors, and reducing their adverse effects. Bifidobacteria shows its multipronged effect by modulating various immunomodulatory and inflammatory signaling pathways, potentially leading to the suppression of tumor growth. Moreover, different species of bifidobacteria are known to regulate signaling molecules involved in promoting apoptosis. In addition, bifidobacteria have an impact on the regulation of diverse microRNAs. The anticancer properties of may also stem from its ability to detoxify carcinogens and transform dietary elements. This review also covers how dietary factors can influence the prevalence of in the gut, further affecting its anticancer capabilities.
The LRIG gene family consists of LRIG1-3. While LRIG2 has been described as a tumor promoter, LRIG1 and LRIG3 have been identified as tumor suppressors in previous literature. Because of these contrasting roles, the expr...The LRIG gene family consists of LRIG1-3. While LRIG2 has been described as a tumor promoter, LRIG1 and LRIG3 have been identified as tumor suppressors in previous literature. Because of these contrasting roles, the expression of LRIG1-3 was examined across different grades of glioma, between primary and secondary glioblastoma and with focus on chemotherapy treatment. Human tumor tissue samples were extracted during neurosurgery and grouped among the WHO classification valid at the time of surgery. Quantitative western blot analysis, qPCR and immunofluorescence staining were performed. LRIG1 was less expressed in glioma compared to peritumoral tissue with additional decrease with ascending tumors grade. Further, secondary glioblastoma expressed more LRIG1 protein than primary. On mRNA level, the same was seen for LRIG2, were low grade glioma expressed significantly more LRIG2 than high grade glioma. And on protein level, secondary glioblastoma showed higher expression than primary. LRIG3 mRNA expression, in contrast, was significantly higher in grade II gliomas compared to surrounding control tissue, whereas chemotherapy did not significantly affect expression levels in glioblastoma. Our results reinforce suggestions that LRIG1-3 could function as diagnostic markers and therapeutic targets in the treatment of gliomas.
In this study, cerium oxide nanoparticles (CeO NPs) were synthesized using a green chemistry approach, utilizing quince fruit (Cydonia oblonga) peel extract as a non-toxic reducing and stabilizing agent. This environment...In this study, cerium oxide nanoparticles (CeO NPs) were synthesized using a green chemistry approach, utilizing quince fruit (Cydonia oblonga) peel extract as a non-toxic reducing and stabilizing agent. This environmentally friendly technique represents a novel approach to nanoparticle fabrication, emphasizing sustainability in nanotechnology. The surface of the green-synthesized CeO NPs was further functionalized with cidofovir (CDV), an anti-DNA virus agent, to develop a dual-functional therapeutic platform with potential anticancer and antiviral applications. The successful synthesis and modification of CDV-loaded CeO NPs (CDV- CeO NPs) were confirmed through a series of characterizations, including FT-IR, zeta potential, TEM, SEM-EDX, DLS, and UV-Vis analyses. The cytotoxic effects of CDV, CeO NPs, and CDV- CeO NPs were evaluated against the MCF-7 breast cancer cell line using the MTT assay, revealing that the loading of CDV onto CeO NPs significantly enhanced its anticancer efficacy. Furthermore, the interaction of CDV-CeO NPs with nucleic acids (DNA and RNA) was investigated through absorption and fluorescence studies, demonstrating a strong binding affinity and suggesting the potential of these nanoparticles as highly specific chemotherapeutic agents. The novelty of this work lies in the innovative green synthesis method, the dual-functional therapeutic application, and the enhanced biological activity of the CDV-CeO NPs, which collectively position these nanoparticles as promising candidates for future cancer and antiviral therapies.
Contemporary fluorescence-guided surgery has evolved principally based on the uses and limitations of the contrast agent indocyanine green (ICG). A second generation of novel fluorescent agents are under development to t...Contemporary fluorescence-guided surgery has evolved principally based on the uses and limitations of the contrast agent indocyanine green (ICG). A second generation of novel fluorescent agents are under development to target specific molecular markers on tumor cells and/or the tumor micro-environment. Pafolacianine, a molecular agent targeting the folate receptor (FR), is the first of these approved for use in adults, but its potential utility in pediatric cancers is unknown. In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors. Slides were stained with antibodies to FRα and FRβ, and fluorescence was quantified. Separately, publicly available RNA sequencing data were queried for both FRα and FRβ expression in various pediatric tumors.
Jimenez H, Gibo D, Sharma S
… +23 more, Pennison M, Miller LD, Wang M, Sheffield K, Zhang L, Johansen A, Achari P, Mcgrath C, Lester S, Tang J, Agyemang K, Johnson A, Whitlow CT, Chan M, Watabe K, D'Agostino R, Liyanage J, Azmi A, Barger G, Barbault A, Lesser GJ, Debinski W, Pasche BC
BACKGROUND: Intrabuccal administration of amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) resulting in the systemic delivery of low and safe levels of AM RF EMF has shown activity in sever...BACKGROUND: Intrabuccal administration of amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) resulting in the systemic delivery of low and safe levels of AM RF EMF has shown activity in several forms of cancer. METHODS: Glioblastoma (GB) cell lines were exposed to GB-specific AM RF EMF (GBMF) three hours per day at a level of exposure identical to patients during treatment. Cellular assays and agnostic genomic approaches were used to characterize the mechanism-of-action. One patient with therapy refractory GB received compassionate use treatment with GBMF as well as a second patient with refractory oligodendroglioma. RESULTS: Treatment with GBMF inhibited the proliferation of several GB cell lines. CACNA1H mediates the effect of GBMF. GBMF modulates the "Mitotic Roles of Polo-Like Kinase" pathway resulting in the disruption of GB mitotic spindle. There was evidence of clinical and radiological benefit in a 38-year-old patient with recurrent GB and evidence of safety and feasibility in a 47-year-old patient with oligodendroglioma. CONCLUSIONS: This is the first report showing antitumor activity, disruption of the mitotic spindle, activation of the Mitotic Roles of Polo-like kinase pathway in GB. This is also the first report showing feasibility and clinical activity in patients with brain tumor.
STACT is a modular, genetically engineered live attenuated Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration....STACT is a modular, genetically engineered live attenuated Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration. It has been engineered to minimize systemic toxicity and to enrich in the tumor microenvironment (TME) via metabolic dependency and showed a decreased systemic inflammatory cytokine profile compared to its parent strain VNP20009. ACTM-838 utilizes the STACT platform to deliver IL-15/IL15Rα and a constitutively active STING to tumor-resident phagocytic antigen-presenting cells. Upon intravenous (IV) dosing to tumor-bearing mice, ACTM-838 distributed and enriched in the TME, exhibited specific uptake in tumor-resident phagocytic cells and led to expression of human IL-15/IL15Rα and murine IFNα in the tumor. ACTM-838 induced comprehensive TME changes to an immune permissive anti-tumor phenotype with a decrease in exhausted T-cells and Tregs and an increase in cytolytic T-cells and MHCII-high proliferating myeloid cells. ACTM-838-treated tumors exhibited upregulated anti-tumor innate and adaptive immunity expression profiles, T-, NK- and B-cell infiltration and downregulated cell cycle, DNA damage and TGFβ responses. Single-cell RNAseq and flow cytometry data confirmed activation and infiltration of both innate and adaptive immune cells. ACTM-838 showed durable anti-tumor efficacy in multiple murine tumor models and synergized with anti-PD1 therapy in combination.