Case Report: Toripalimab: a novel immune checkpoint inhibitor in advanced nasopharyngeal carcinoma and severe immune-related colitis

Toripalimab, a specific immune checkpoint inhibitor targeting the programmed death 1 (PD-1) receptor, represents a novel immunotherapeutic approach for advanced nasopharyngeal carcinoma, showing promising curative potential. However, it is not without drawbacks, as some patients experience immune-related adverse events (irAEs) associated with this treatment, and there remains a limited body of related research. Here, we present a case of advanced nasopharyngeal carcinoma in a patient who developed colitis as an irAE attributed to Toripalimab. Subsequent to Toripalimab treatment, the patient achieved complete remission. Notably, the development of colitis was accompanied by inflammatory manifestations evident in colonoscopy and pathology results. Further investigation revealed cytomegalovirus (CMV) infection, detected through immunohistochemistry in 11 colon biopsies. Subsequent treatment with ganciclovir and steroids resulted in symptom relief, and colonoscopy indicated mucosal healing. Our case highlights the association between irColitis induced by Toripalimab and CMV infection. Toripalimab demonstrates remarkable efficacy in treating advanced nasopharyngeal carcinoma, albeit with a notable risk of irAEs, particularly in the form of colitis. The link between symptoms and endoscopic pathology findings in irColitis is noteworthy. Standardized biopsy procedures can effectively confirm the diagnosis of CMV infection. Our findings may provide valuable guidance for managing acute CMV infection and irAEs associated with Toripalimab in the treatment of nasopharyngeal carcinoma in the future

Second primary colorectal cancer in adults: a SEER analysis of incidence and outcomes

Abstract Background At present, there was no large epidemiological study exploring the actual incidence and survival of second primary colorectal cancer (spCRC). The different characteristics and survival of patients with spCRC and initial primary colorectal cancer (ipCRC) still need to be elucidated. In addition, the factors leading to different survival status of spCRC and ipCRC were still unclear. Our study plan to explore the annual incidence trend of spCRC as well as the factors influencing the occurrence and survival outcome of spCRC. Methods This cohort study analyzed the data of 4680 spCRC patients and 330,937 initial primary colorectal cancer (ipCRC) patients. Whether patients had spCRC and whether spCRC patients survived or died were regarded as outcomes. The annual incidence of spCRC from 2004 to 2016 was analyzed by Jointpoint regression analysis. The truncation points were found, and the annual percentage change (APC) of each segment was calculated to explore the trend of spCRC change in the United States. Univariate and multivariable cox regression analyses were conducted to identify factors associated with the occurrence and prognosis of spCRC patients. Results The total incidence of spCRC was decreased during 2000–2016 on the whole. The overall incidence of spCRC was lowered in both males and females despite 2013–2014, in the left colon, right colon, rectum and others. The incidence of spCRC was decreased in both 18–49 years’ people and ≥ 50 years’ people during 2000–2016, and the incidence of spCRC in the ≥ 50 years’ people group was higher than those of 18–49 years. Insured (OR = 0.867 (0.778–0.966), initial primary site of other digestive (OR = 0.46, 95%CI: 0.42–0.50), rectum (OR = 0.74, 95%CI: 0.66–0.82), or right colon (OR = 0.73, 95%CI: 0.68–0.79), N 1 stage (OR = 0.87, 95%CI: 0.76–0.99), M 1 stage (OR = 0.49, 95%CI: 0.30–0.80), AJCC II stage (OR = 0.70, 95%CI: 0.60–0.82), AJCC III stage (OR = 0.69, 95%CI: 0.56–0.84), and radiation (OR = 0.69, 95%CI: 0.57–0.83) were associated with the risk of spCRC. At the end of follow-up, 2,246 spCRC patients were survived and 2,434 spCRC patients were dead. Patients with spCRC had poor survival probability than patients with ipCRC. Older age (HR = 1.02, 95%CI: 1.02–1.03), male (HR = 1.13, 95%CI: 1.04–1.23), Black (HR = 1.20, 95%CI: 1.06–1.35), uninsured (HR = 1.36, 95%CI: 1.16–1.59), Signet ring cell carcinoma (HR = 1.64, 95%CI: 1.19–2.25), T4 stage (HR = 1.63, 95%CI: 1.32–2.01), N2 stage (HR = 1.36, 95%CI: 1.08–1.72), M1 stage (HR = 4.51, 95%CI: 2.00–10.18), AJCC III (HR = 1.47, 95%CI: 1.08–1.98), and radiation (HR = 1.82, 95%CI: 1.43–2.33) were associated with increased risk of mortality in spCRC patients. Conclusion The incidence of spCRC was decreased except in people with initial primary tumor grade IV and those aged 15–39 years. The overall survival of spCRC patients was lower than ipCRC patients. Cancer patients with older age, high tumor grade, TNM stage, and AJCC stage should be caution to the occurrence of spCRC and timely interventions should be provided for spCRC patients to improve their outcomes

Antioxidant Therapy in Cancer: Rationale and Progress

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances and signaling aberrations, can promote carcinogenesis and malignant progression by inducing gene mutations and activating pro-oncogenic signaling, providing a possible rationale for targeting oxidative stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy in cancer remains unproven. Here, we review the rationale for, and recent advances in, pre-clinical and clinical research on antioxidant therapy in cancer, including targeting ROS with nonenzymatic antioxidants, such as NRF2 activators, vitamins, N-acetylcysteine and GSH esters, or targeting ROS with enzymatic antioxidants, such as NOX inhibitors and SOD mimics. In addition, we will offer insights into prospective therapeutic options for improving the effectiveness of antioxidant therapy, which may expand its applications in clinical cancer treatment

Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy

Abstract Emerging evidence indicates that cancer cells can mimic characteristics of embryonic development, promoting their development and progression. Cancer cells share features with embryonic development, characterized by robust proliferation and differentiation regulated by signaling pathways such as Wnt, Notch, hedgehog, and Hippo signaling. In certain phase, these cells also mimic embryonic diapause and fertilized egg implantation to evade treatments or immune elimination and promote metastasis. Additionally, the upregulation of ATP‐binding cassette (ABC) transporters, including multidrug resistance protein 1 (MDR1), multidrug resistance‐associated protein 1 (MRP1), and breast cancer‐resistant protein (BCRP), in drug‐resistant cancer cells, analogous to their role in placental development, may facilitate chemotherapy efflux, further resulting in treatment resistance. In this review, we concentrate on the underlying mechanisms that contribute to tumor development and progression from the perspective of embryonic development, encompassing the dysregulation of developmental signaling pathways, the emergence of dormant cancer cells, immune microenvironment remodeling, and the hyperactivation of ABC transporters. Furthermore, we synthesize and emphasize the connections between cancer hallmarks and embryonic development, offering novel insights for the development of innovative cancer treatment strategies

Metastasis organotropism in colorectal cancer: advancing toward innovative therapies

Abstract Distant metastasis remains a leading cause of mortality among patients with colorectal cancer (CRC). Organotropism, referring to the propensity of metastasis to target specific organs, is a well-documented phenomenon in CRC, with the liver, lungs, and peritoneum being preferred sites. Prior to establishing premetastatic niches within host organs, CRC cells secrete substances that promote metastatic organotropism. Given the pivotal role of organotropism in CRC metastasis, a comprehensive understanding of its molecular underpinnings is crucial for biomarker-based diagnosis, innovative treatment development, and ultimately, improved patient outcomes. In this review, we focus on metabolic reprogramming, tumor-derived exosomes, the immune system, and cancer cell-organ interactions to outline the molecular mechanisms of CRC organotropic metastasis. Furthermore, we consider the prospect of targeting metastatic organotropism for CRC therapy

Exploiting Polyphenol-Mediated Redox Reorientation in Cancer Therapy

Polyphenol, one of the major components that exert the therapeutic effect of Chinese herbal medicine (CHM), comprises several categories, including flavonoids, phenolic acids, lignans and stilbenes, and has long been studied in oncology due to its significant efficacy against cancers in vitro and in vivo. Recent evidence has linked this antitumor activity to the role of polyphenols in the modulation of redox homeostasis (e.g., pro/antioxidative effect) in cancer cells. Dysregulation of redox homeostasis could lead to the overproduction of reactive oxygen species (ROS), resulting in oxidative stress, which is essential for many aspects of tumors, such as tumorigenesis, progression, and drug resistance. Thus, investigating the ROS-mediated anticancer properties of polyphenols is beneficial for the discovery and development of novel pharmacologic agents. In this review, we summarized these extensively studied polyphenols and discussed the regulatory mechanisms related to the modulation of redox homeostasis that are involved in their antitumor property. In addition, we discussed novel technologies and strategies that could promote the development of CHM-derived polyphenols to improve their versatile anticancer properties, including the development of novel delivery systems, chemical modification, and combination with other agents

Laser-activatable oxygen self-supplying nanoplatform for efficiently overcoming colorectal cancer resistance by enhanced ferroptosis and alleviated hypoxic microenvironment

Abstract Background Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemo-resistance remaining a major obstacle in CRC treatment. Notably, the imbalance of redox homeostasis-mediated ferroptosis and the modulation of hypoxic tumor microenvironment are regarded as new entry points for overcoming the chemo-resistance of CRC. Methods Inspired by this, we rationally designed a light-activatable oxygen self-supplying chemo-photothermal nanoplatform by co-assembling cisplatin (CDDP) and linoleic acid (LA)-tailored IR820 via enhanced ferroptosis against colorectal cancer chemo-resistance. In this nanoplatform, CDDP can produce hydrogen peroxide in CRC cells through a series of enzymatic reactions and subsequently release oxygen under laser-triggered photothermal to alleviate hypoxia. Additionally, the introduced LA can add exogenous unsaturated fatty acids into CRC cells, triggering ferroptosis via oxidative stress-related peroxidized lipid accumulation. Meanwhile, photothermal can efficiently boost the rate of enzymatic response and local blood flow, hence increasing the oxygen supply and oxidizing LA for enhanced ferroptosis. Results This nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models. Conclusions Taken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance. Graphical Abstrac

Precise Control of π-electron Magnetism in Metal-free Porphyrins

The porphyrin marcocycle can stabilize a set of magnetic metal ions, thus introducing localized net spins near the center. However, it remains illusive but most desirable to introduce delocalized spins in porphyrins with wide implications, for example, for building correlated quantum spins. Here, we demonstrate that metal-free porphyrins host delocalized π-electron magnetism as revealed by scanning probe microscopy and different level of theory calculations. Our results demonstrate that engineering of π-electron topologies introduces spin polarized singlet state and delocalized net spins in metal-free porphyrins. In addition, the π-electron magnetism can be switched on/off via STM manipulation by tunning the interfacial charge transfer. Our results provide an effective way to precisely control the π-electron magnetism in metal-free porphyrins, which can be further extended to design new magnetic functionalities of porphyrin-based architectures