Oncotarget最新文献

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 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 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: In vitro 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 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. E2F8, WDR77, and hsa-miR-495-3p 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.

Bifidobacterium has captured major attention recently because of its health benefits and extensive research highlighting its potential in cancer treatment and prevention. Evidence suggests that bifidobacterium can actively fight against various types of cancer, including those of the colon, lungs, breast, and stomach. Research indicates that several species of bifidobacterium 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 bifidobacterium 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 bifidobacterium in the gut, further affecting its anticancer capabilities.

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.