Cancer Medicine最新文献_第2页

Bridging Cancer and COVID-19: The Complex Interplay of ACE2 and TMPRSS2

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70829

Xuerui Tang, Liuzhi Lu, Xiaoping Li, Panpan Huang

The coronavirus disease 2019 (COVID-19) pandemic presents heightened risks for cancer patients, who are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes due to immunosuppression from both the malignancy and anticancer therapies. This review investigates the dual roles of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in SARS-CoV-2 infection among cancer patients. ACE2, the vital entry receptor for SARS-CoV-2, is overexpressed in certain tumors such as colon adenocarcinoma, renal carcinomas, pancreatic adenocarcinoma, and lung adenocarcinoma, potentially increasing viral susceptibility. Paradoxically, ACE2 also exhibits tumor-suppressive properties by inhibiting angiogenesis and modulating the tumor microenvironment, leading to improved patient prognoses in some cancers like breast cancer. TMPRSS2, essential for viral entry, shows decreased expression in several tumors but acts as a prognostic biomarker in prostate and lung cancers. This review illustrates the complexity of therapeutically targeting ACE2 and TMPRSS2 due to their contrasting roles in cancer progression and viral entry. We analyze the expression levels of ACE2 and TMPRSS2 in relation to immune cell infiltration and patient outcomes, and propose personalized therapeutic strategies. Furthermore, we underscore the necessity for multidisciplinary approaches, integrating antiviral treatments with cancer therapies and tailoring interventions based on individual molecular profiles. This approach to personalized medicine seeks to enhance treatment results and better manage cancer patients who have contracted SARS-CoV-2.

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引用次数: 0

Exploring the Dynamics of Immune Checkpoint Inhibitor-Induced Eosinophilia in Advanced/Metastatic Melanoma: A Comprehensive Retrospective Analysis

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70679

Panagiotis T. Diamantopoulos, Aikaterini Gkoufa, Amalia Anastasopoulou, Panagiotis Kouzis, Georgios Lyrarakis, Georgios Kyriakakis, Helen Gogas

Background

Immune-related eosinophilia has emerged as an adverse event associated with immune checkpoint inhibitors (ICIs). Its prevalence, severity, duration, clinical significance, diagnostic approach, and management remain unexplored.

Methods

We conducted a retrospective review of melanoma patient records at a university referral center. Our analysis encompassed the incidence of eosinophilia, baseline disease characteristics, treatment modalities, peak eosinophil counts, associated symptoms, diagnostic procedures, management strategies, disease course, and prognostic implications.

Results

A total of 308 patients were included. Eosinophilia was present in 21.4%, and there was no association with gender, age, histologic type, stage, or BRAF mutation status. The median time interval from treatment initiation to the eosinophilia onset was 56 days, the median eosinophil count at first presentation was 0.70 × 10⁹/L, and the maximum eosinophil count was 1.02 × 10⁹/L. The rate of eosinophilia was significantly higher in patients treated with nivolumab plus bempegaldesleukin (50.0%), followed by nivolumab plus ipilimumab (21.7%). Symptomatic patients and/or patients with hypereosinophilia were assessed for organ involvement and for the identification of the cause of eosinophilia. Patients requiring medical intervention were managed with corticosteroids or antihistamines. Eosinophilia relapsed in 31.8% when rechallenged. While non-significant, there was a numeric trend for longer overall survival in patients with eosinophilia (42.6 vs. 27.9 months, p = 0.178).

Conclusions

This study marks the first comprehensive approach of the relationship between the type of immunotherapy and the incidence of eosinophilia in melanoma patients. It also delves into the patients' baseline characteristics, diagnostic assessment, management, and prognosis, providing useful guidance for physicians treating patients with ICIs.

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引用次数: 0

Visceral Adipose Predicts Prognosis and Toxicities in Locally Advanced Bladder Cancer Patients Treated With Adjuvant Gemcitabine Plus Cisplatin Chemotherapy

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70742

Zhimin Gao, Lei Zhang, Zhen Li, Xu Qin, Zewei Wang, Junqi Wang, Nienie Qi, Hailong Li

Purpose

For patients with bladder cancer (BC) undergoing radical cystectomy followed by adjuvant chemotherapy, the impact of visceral adipose tissue on prognosis and chemotherapy-related toxicities has not been well established.

Materials and Methods

From July 2013 to November 2020, 224 BC patients received adjuvant gemcitabine plus cisplatin at our institution. Computed tomography images of the patients were analyzed to calculate the visceral adipose tissue index (VATI). Patients were stratified into high- and low-VATI groups based on a predetermined cutoff value, and differences in prognosis and chemotherapy-related adverse events (AEs) between the two groups were compared.

Results

After propensity score matching, a total of 166 patients were enrolled, with 83 in the low-VATI group and 83 in the high-VATI group. The low-VATI group exhibited notably extended progression-free survival (PFS) in comparison to the high-VATI group (p = 0.044). Conversely, no substantial variation was noted concerning overall survival (OS) among the patient cohorts. In the multivariable Cox regression analysis, patients aged over 70 years (HR = 1.66, 95% CI 1.09–2.57, p = 0.04) and nodal positivity (HR = 2.98, 95% CI 1.04–4.28, p = 0.01) emerged as significant risk factors for OS. In addition to the level of VATI (HR = 2.47, 95% CI 1.02–4.21, p = 0.04), nodal positivity (HR = 4.04, 95% CI 1.30–12.56, p = 0.02) remained a significant risk factor for PFS. Regarding chemotherapy-related AEs, the most common AEs of any grade and grade ≥ 3 were hematologic toxicities. Patients in the low-VATI group exhibited a higher likelihood of experiencing grade ≥ 3 neutropenia compared to those in the high-VATI group (p = 0.04).

Conclusions

This study demonstrated that, among patients treated with adjuvant chemotherapy for locally advanced BC, patients in the low-VATI group exhibited a significantly prolonged PFS compared to those in the high-VATI group. However, no significant difference was observed in terms of OS. Regarding chemotherapy-related AEs, patients in the high-VATI group exhibited a relatively lower incidence and severity of toxic reactions.

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引用次数: 0

KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70731

Yanming Hu, Jing Zhou, Xinru Ling, Kun Zhao, Peng Huang, Max Gao, Xiaoqing Li, Ming Sun, Yanfen Zou, Guannan Feng

Background

Abnormal protein localization due to disrupted nucleoplasmic transport is common in tumor cells, but its mechanisms are not well understood. Nuclear pore complexes and nuclear transporter proteins are crucial for protein transport between the nucleus and cytoplasm. Evidence increasingly shows that abnormal expression of karyopherin family proteins disrupts protein translocation, affecting processes like cell differentiation, proliferation, apoptosis, and transcriptional regulation. However, their functions and roles in ovarian cancer remain unclear.

Methods

The expression level of KPNA5 in ovarian cancer tissues and cells was detected by IHC, Western blot, and qPCR. CCK-8 and colony formation assays were used to assess cell proliferation ability. Transwell assay was conducted to determine cell migration and invasion capacity. A xenograft model was used to assess the effect of KPNA5 on tumor growth in vivo.

Results

KPNA5 expression is downregulated in ovarian cancer (OC) tissues. Low KPNA5 levels were associated with poor survival in OC patients, validated by an OC tissue sample cohort. Overexpression of KPNA5 significantly suppressed OC cell proliferation, tumor growth, and invasion in both in vitro and in vivo studies. Mechanistically, KPNA5 recognizes nuclear localization signals (NLSs) in PTPN4, mediating its nuclear transport and inhibiting STAT3 phosphorylation and its downstream signaling pathway. Similarly, PTPN4 overexpression reduced OC cell viability and invasion, also suppressing STAT3 phosphorylation.

Conclusions

Our findings identify KPNA5 as a tumor suppressor in OC, presenting a potential therapeutic target for OC treatment.

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引用次数: 0

Chemokines: Orchestration of the Tumor Microenvironment and Control of Hepatocellular Carcinoma Progression

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70789

Jiezuan Yang, Haifeng Lu, Lanjuan Li

Chemokines, a family of chemotactic cytokines, play a central role in shaping the tumor microenvironment (TME) and in influencing the progression of hepatocellular carcinoma (HCC), a well-known inflammation-related cancer. This review addresses the intricate interplay between chemokines and HCC and highlights their multifaceted role. We discuss how altered expression of chemokines within the TME contributes to the development of HCC by orchestrating the recruitment of immune cells, ultimately leading to immunosuppression. In addition, we are investigating the contribution of chemokines to important features of HCC progression, including angiogenesis and epithelial-mesenchymal transition (EMT). The potential of chemokines as serum biomarkers for HCC diagnosis and their potential as novel therapeutic targets are also explored. This comprehensive review emphasizes the importance of chemokines in the pathogenesis of HCC and their potential for a better understanding and treatment of this difficult disease.

引用次数: 0

Characterization of the Pancreatic Neuroendocrine Neoplasm Immune Microenvironment

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70798

Filipe Reis Neves, Ana Luís Martins, Rui Caetano Oliveira, Rui Martins

Introduction

A tumor is composed of more than tumoral cells. In recent years, there has been an increase in interest and knowledge of the tumor microenvironment (TME).

Methods

The TME is an integral part of the tumor, composed of several cells: immune, stromal, and endothelial, among others, thus offering a wide range of tumor interactions and multiple possibilities for targeted therapies and environment modulation. While the TME in pancreatic ductal adenocarcinoma is widely studied, it is not very true for the TME of pancreatic neuroendocrine neoplasms (PNENs).

Discussion and Conclusion

The incidence of PNENs is increasing and, therefore, it is important to comprehend their biology for the evolution of efficient therapies since many of the PNENs develop metastasis, including the G1 PNENs. This paper focuses on a review of the role of the TME in PNENs.

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引用次数: 0

Overall Survival With Palbociclib and Aromatase Inhibitor Versus Aromatase Inhibitor Alone in Older Patients With HR+/HER2− Metastatic Breast Cancer

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70719

Adam M. Brufsky, Rickard Sandin, Stella Stergiopoulos, Connie Chen, Siddharth Karanth, Benjamin Li, Elizabeth Esterberg, Doris Makari, Sean D. Candrilli, Ravi K. Goyal, Hope S. Rugo

Introduction

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the current standard of care for first-line (1L) treatment of hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC). To investigate the effectiveness of palbociclib, the first-in-class CDK4/6i, plus an aromatase inhibitor (AI) in older patients, we compared overall survival (OS) in a Medicare population treated with 1L palbociclib + AI versus an AI alone.

Methods

Patients aged ≥ 65 years who were diagnosed with de novo HR+/HER2– mBC from 2015 to 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER)–linked Medicare database and were eligible if they initiated 1L palbociclib + AI or an AI alone. The primary endpoint was OS. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance baseline patient characteristics.

Results

Of 779 eligible patients, 296 received palbociclib + AI and 483 received AI alone as 1L treatment. After sIPTW, the median follow-up was 23.1 months with palbociclib + AI and 18.2 months with AI alone. Adjusted median OS was longer with palbociclib + AI versus AI alone (sIPTW: 37.6 vs. 25.5 months, HR = 0.73 [95% CI, 0.59–0.91]). In multivariable Cox proportional hazards regression, patients treated with palbociclib + AI versus AI alone had a 39% lower risk of death (HR = 0.61 [95% CI, 0.48–0.77]).

Conclusion

In routine US clinical practice, palbociclib + AI was associated with significantly prolonged OS versus AI alone in 1L treatment of patients aged ≥ 65 years with de novo HR+/HER2– mBC, adding to the growing body of evidence on the survival benefit of palbociclib + AI in this patient population.

Trial Registration

ClinicalTrials.gov identifier: NCT06086340

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引用次数: 0

Patterns of Clinical Trial Enrollment for Pediatric Patients With Hepatoblastoma and Wilms Tumor: A Report From the Children's Oncology Group

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70692

Pablo S. Monterroso, Sarah Lucht, Jeannette M. Sample, Angela D. Trobaugh-Lotrario, Helen M. Parsons, Lucie M. Turcotte, David Van Riper, Jenny N. Poynter, Erin L. Marcotte

Background

Published childhood cancer studies have observed differences in therapeutic trial enrollment by race, ethnicity, socioeconomic status (SES), and age at diagnosis. Our study investigates patterns of enrollment for pediatric oncology clinical trials.

Methods

We analyzed differences in Children's Oncology Group clinical trial enrollment in a cohort of pediatric patients with hepatoblastoma (n = 212) and Wilms tumor (n = 1107). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated for trial enrollment by patient characteristics. Odds ratios (ORs) and 95% CIs were estimated to examine associations between characteristics and three outcomes (therapeutic trial [referent], exclusively non-therapeutic study, no trial or study). Statistical significance tests were two-sided.

Results

Approximately half of all cases enrolled in therapeutic trials for both tumor types (Wilms: 48%; hepatoblastoma: 51%). For Wilms tumor, patients diagnosed at ages 3–5 years were more likely to enroll compared to those diagnosed at age < 1 year (RR = 1.06; 95% CI = 1.01, 1.13) and had lower odds of joining exclusively a non-therapeutic study compared to those diagnosed at age < 1 years (OR = 0.63; 95% CI = 0.44, 0.90). There was no association between race, ethnicity, or SES and enrollment. For hepatoblastoma, no variables indicated any statistically significant difference in enrollment.

Conclusions

Few differences in clinical trial enrollment were observed during periods when trials were available for all risk groups, a promising sign of equity in pediatric oncology clinical trial recruitment. Among Wilms tumor cases, differences in enrollment were observed for age at diagnosis, a potential proxy for disease acuity, which may influence decision making.

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引用次数: 0

The Role of Cholesterol Metabolism and Its Regulation in Tumor Development

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70783

Yongmei Wu, Wenqian Song, Min Su, Jing He, Rong Hu, Youbo Zhao

Background

Within the tumor microenvironment, tumor cells undergo metabolic reprogramming of cholesterol due to intrinsic cellular alterations and changes in the extracellular milieu. Furthermore, cholesterol reprogramming within this microenvironment influences the immune landscape of tumors, facilitating immune evasion and consequently promoting tumorigenesis. These biological changes involve modifications in numerous enzymes associated with cholesterol uptake and synthesis, including NPC1L1, SREBP, HMGCR, SQLE, and PCSK9.

Review

This review systematically summarizes the role of cholesterol metabolism and its associated enzymes in cancer progression, examines the mechanisms through which dysregulation of cholesterol metabolism affects immune cells within the tumor microenvironment, and discusses recent advancements in cancer therapies that target cholesterol metabolism.

Conclusion

Targeting cholesterol metabolism-related enzymes can inhibit tumor growth, reshape immune landscapes, and rejuvenate antitumor immunity, offering potential therapeutic avenues in cancer treatment.

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引用次数: 0

Comparative Efficacy of Various Exercise Types on Cancer-Related Fatigue for Cancer Survivors: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-03-27 DOI: 10.1002/cam4.70816

Shichen Zhou, Guang Chen, Xiaoyu Xu, Cheng Zhang, Guoming Chen, Yau-Tuen Chan, Ya Xuan Sun, Jiayan Zhou, Ning Wang, Yibin Feng

Background

This study compares the effectiveness of 7 types of guideline-recommended first-line exercises for cancer-related fatigue (CRF).

Methods

A comprehensive search was conducted utilizing public databases, including Medline, Embase, Web of Science, and Cochrane Library. Randomized clinical trials examining the effects of aerobic exercise, resistance exercise, stretching exercise, combined aerobic and resistance exercise, Yoga, Qigong, or Tai Chi on CRF in various cancer types were included. A Bayesian network meta-analysis was used to synthesize the data. Subgroup analyses and sensitivity analyses were used to detect the effect modifiers and to confirm the robustness, respectively.

Results

A total of 33 clinical trials were included in this analysis. Overall, both resistance (SMD, −1.72; 95% CI, −2.81 to −0.63) and Yoga (SMD, −1.27; 95% CI, −1.38 to −1.16) reduced the fatigue severity significantly better than standard care, but there was no significant decrease for other exercise types. For cancer survivors with an age over 55 years, only Yoga showed statistically significant improvement in CRF (SMD, −1.27; 95% CI, −1.38 to −1.16). For patients with an age less than 55 years, both resistance (SMD, −1.75; 95% CI, −2.91 to −0.58) and Yoga (SMD, −1.66; 95% CI, −2.81 to −0.51) reduced the fatigue severity compared to standard care.

Conclusion

Both resistance exercise and yoga showed significant benefits in alleviating CRF compared to standard care. Yoga was particularly effective for cancer survivors over 55 years of age, while resistance exercise and yoga were comparably effective for those under 55 years.

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引用次数: 0