Onco, Volume 5, Issue 2 (June 2025) – 13 articles

Tumor cells and the tumor microenvironment (TME) produce factors, including neurotrophins, that induce axonogenesis and neurogenesis, and increase local nerve density. Proliferative growing cancer cell clusters and disseminated invasive tumor cells undergoing partial epithelial-to-mesenchymal transition (pEMT) can invade peripheral nerves. In the early stages of tumor–nerve interactions, Schwann cells (SCs) dedifferentiate, become activated and migrate to cancer cell nests; later, they induce pEMT in tumor cells and activate tumor cell migration along nerves. The SC–tumor–nerve interaction attracts myeloid-derived suppressor cells (MDSCs) and inflammatory monocytes, and the latter differentiate into macrophages. SCs and MDSCs are responsible for the activation of transforming growth factor-beta (TGF-beta) signaling. Intra-tumoral innervation is followed by perineural invasion (PNI), which has an unfavorable prognosis. What are the interventional options against PNI: local reduction in tumor nerves or inhibition of TGF-beta-related events, inhibition of downstream signaling of TGF-beta or immune activation, or intervention against immunosuppression? This systematic review is based on the Prisma 2009 search method and provides an overview of tumor–nerve interaction. Full article

Globally, women’s cancer-related morbidity and death are still caused mainly by gynecologic cancer. Antioxidant and anti-inflammatory drugs have shown promise in treating gynecologic cancer because of the complex interactions among oxidative stress, inflammation, and the development of tumors. This review focuses on how these drugs, which include polyphenols, terpenoids, and thiols-related phytochemical-derived compounds target different pathways associated with developing and progressing gynecologic cancer. We investigate what factors affect the tumor microenvironment, specifically how they affect immunological response and vasculogenesis. Through the review of recent studies, we have gained an extensive understanding of the molecular pathways that anti-inflammatory and antioxidant drugs use to achieve their therapeutic benefits. Gynecologic cancer is still a potent cause of cancer-related deaths and fatalities for women globally. Antioxidant and anti-inflammatory drugs have shown promise in treating gynecologic cancer because of the complex interactions among oxidative stress, inflammation, and the development of tumors. This review focuses on how these drugs target different pathways associated with developing and progressing gynecologic cancer. We investigate what factors affect the tumor microenvironment, specifically how they affect immunological response and vasculogenesis. Through the review of recent studies, we have gained an extensive understanding of the molecular pathways that anti-inflammatory and antioxidant drugs use to achieve their therapeutic benefits. Full article

Approximately 5.4 million nonmelanoma skin cancers are treated each year in the US. Of this number 80 to 90% are basal cell carcinomas. In this study, we compare optical coherence tomography (OCT) images and vibrational optical coherence tomography (VOCT) measurements made on small and large nodular basal cell carcinomas (BCCs) using histopathology, OCT images, and VOCT physical measurements. OCT images were broken into green, blue, and red subchannel images and compared to histopathology conducted on the excised tissue. While our results suggest that both small and large BCCs have similar morphologies that include circular nodules with palisading cells surrounding the lesions, no part of the excised lesions appeared like normal skin. In the small lesion, the nodule is surrounded by tissue that may be considered to have “clear” margins even though the rete ridges are missing, and the ECM does not resemble normal skin. The edges of the lesion are free of palisading cells with only some inflammatory cells being present. In contrast, the mechanovibrational spectrum of the large lesion appeared to have an increased amount of large fibrotic peaks with decreased vibrations for normal cells and cancer-associated fibroblasts compared to the smaller nodule. These results indicate that it is possible to identify the location of the BCC nodules noninvasively using VOCT. The ability to noninvasively identify nodular BCCs using this technique makes it a useful adjunct to visual inspection and dermoscopy to identify cancerous lesions seen in the clinic. Since VOCT can be operated remotely, it can serve as a noninvasive screening tool to be used by general practitioners in areas where dermatologists are in short supply. Full article

Background: Our goal was to assess the diagnostic performance of the IOTA 3-step strategy for discriminating benign from malignant adnexal masses. Methods: Systematic review and meta-analysis design. A systematic search across three databases (Medline [PubMed], SCOPUS, and Web of Science) was conducted to identify primary studies reporting on the use of the IOTA three-step strategy from January 2012 to July 2024. Prospective cohort studies utilizing the three-step strategy, with histologic diagnosis or conservative management confirming spontaneous resolution or persistence in cases of benign-appearing masses for at least one year of follow-up, were used as the reference standard. Studies unrelated to the topic, those not addressing the IOTA three-step strategy, studies focusing on other prediction models, letters to the editor, commentaries, narrative reviews, consensus documents, and studies lacking data for constructing a 2 × 2 table were excluded. Quantitative synthesis was done, calculating the pooled sensitivity, specificity, and positive and negative likelihood ratios. Qualitative synthesis was done using QUADAS-2. Results: A total of 448 citations were initially identified, with 7 studies meeting inclusion criteria, comprising 5722 patients. The mean prevalence of ovarian malignancy was 28%. The quality of the studies was considered good. IOTA 3-step strategy showed a pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the three-step strategy for adnexal mass classification were 94% (95% CI = 91–95%), 94% (95% CI = 91–97%), 17.0 (95% CI = 10–28.8), and 0.07 (95% CI = 0.05–0.1), respectively. Heterogeneity for sensitivity was moderate, and for specificity it was high. Conclusions: We conclude that the three-step strategy has good diagnostic performance, reducing the need for expert examiner evaluation. Full article

Background/Objectives: Multiple myeloma is a malignancy of plasma cells detected in the bone marrow, inducing symptoms like anemia, hypercalcemia, renal problems, and bone fractures in multiple myeloma patients, affecting their quality of life. The bone marrow microenvironment plays a crucial role in the prognosis and progression of the disease. The purpose of this study was to examine the relationship between the percentages of the major cell populations of the bone marrow, including immune cells, and physical function/quality of life in multiple myeloma patients after first-line treatment. Methods: Twenty-one multiple myeloma patients (N = 14 men, N = 7 women) participated in the study after completing first-line treatment. Bone marrow and blood samples were taken one hundred days after transplantation, while physical function (6 min walking test, handgrip test, maximal aerobic power, and isometric strength), health-related quality of life (QLQ-C30), and body composition (DXA) were assessed 2–5 days later. Flow cytometry was used to assess the percentages of plasma cells, mast cells, B cells (total, precursors, naïve, and memory), T cells (total, CD27− and CD27+), NK/NKT cells (total, CD27− and CD27+), eosinophils, monocytes, neutrophils, myeloid progenitors, erythroblasts, and erythroid progenitors, expressed as percentages of total nucleated cells of the bone marrow. Results: The percentage of CD27+ NK/NKT cells was correlated with five parameters of the quality of life questionnaire: physical function (r = 0.78, p = 0.005), role functioning (r = 0.69, p = 0.020), fatigue (r = −0.86, p = 0.000), pain (r = 0.68, p = 0.021), and dyspnea (r = −0.80, p = 0.003). Conclusions: In conclusion, stronger immune surveillance in the bone marrow from CD27+ NK/NKT cells is correlated with better quality of life in multiple myeloma patients. Full article

Background: Adult granulosa cell tumours (AGCT) of the ovary account for 2–5% of ovarian tumours, with 30% occurring in women of childbearing age. Despite a good prognosis, up to 25% recur. There is a paucity of high-quality evidence to guide management. Objective: To describe management of AGCT across multiple gynaecological cancer centres. Methods: Retrospective analysis of electronic patient records from six gynaecological cancer centres in Southwest England between 2000 and 2021 (n = 119). Results: We included 107 patients with a median follow-up of 60 months (0–261 months). Most (97/107; 90.7%) were diagnosed with stage I disease (31.8% stage Ic). Primary management was staging surgery in 33/107 (30.8%), hysterectomy and bilateral salpingo-oophorectomy (BSO) (28/107; 26.2%), or conservation of an ovary (17/107; 15.9%). Three had a subsequent pregnancy. A quarter (27/107; 25.2%) were diagnosed with recurrent disease. Fifteen patients (15/107; 14%) had multiple recurrences. Recurrence was more likely if cyst rupture was reported at surgery (38.7%) compared with no rupture (14.3%; p < 0.001). The recurrence rate was higher with ovarian conservation (6/17; 35.3%) compared with BSO (21/90; 23.3%; p < 0.01), and all recurrences involved the residual ovary. Of the 11 deaths, 6 (54.5%) were attributed to progressive disease. Conclusions: Although survival with early-stage disease is good, ovarian cystectomy or unilateral ovarian conservation was associated with increased risk of recurrence. There is no conclusive evidence to support a contralateral oophorectomy in pre-menopausal women, but completion surgery should at least be considered, either immediately or after childbearing/assisted reproductive treatment. Full article

Background: Adult B-cell acute lymphoblastic leukaemia (aB-ALL) is characterised by abnormal differentiation and proliferation of lymphoid progenitors. Despite a significant improvement in relapse-free and overall survival for children with B-ALL, aB-ALL has a particularly poor prognosis with a 5-year survival rate of 20%. First remission is achieved for most patients, but relapse is common with a high associated mortality. New treatments such as immunotherapy offer an opportunity to extend remission and prevent relapse. Methods: aB-ALL antigens were identified using different sources—immunoscreening, protoarrays, two microarrays and one cancer-testis antigen database, and a review of the genomic analyses of aB-ALL. A total of 385 aB-ALL-associated gene products were examined for their association with patient survival. Results: We identified 87 transcripts with differential expression between aB-ALL and healthy volunteers (peripheral blood, bone marrow and purified CD19⁺ cells), and 42 that were associated with survival. Enrichr analysis showed that the Transforming Growth Factor-β (TGFβ), Wnt and Hippo pathways were highly represented (p < 0.02). We found that SOX4 and ROCK1 were upregulated in all types of B-ALL (ROCK1 having a p < 0.001 except in t(8;14) patients), as well as SMAD3 and TEAD4 upregulation being associated with survival (p = 0.0008, 0.05 and 0.001, respectively). Expression of each aB-ALL antigen was verified by qPCR, but only TEAD4 showed significant transcript upregulation in aB-ALL compared to healthy volunteer CD19+ cells (p = 0.01). Conclusions: We have identified a number of antigens and their pathways that play key roles in aB-ALL and may act as useful targets for future immunotherapy strategies. Full article

Breast cancer is a complex disease that is one of the leading causes of cancer-related mortality in women worldwide. Of the subtypes of breast cancer, the most aggressive subtype is triple negative breast cancer (TNBC) due to its lack of targets that could be leveraged for treatment in other subtypes. Current treatment options for both local and metastatic TNBC include radiation therapy, chemotherapy, surgery, targeted therapy, and immunotherapy, which has been gaining popularity in recent years. The role of targeted therapy in TNBC is somewhat limited due to the paucity of therapeutic personalized targets, and, due to the heterogeneity of the disease, the effectiveness of these different modalities varies from patient to patient. These unique elements are the foundation of personalized medicine where genomics and transcriptomics play a critical role in increasing granularity in patients’ disease and treatment. The purpose of these molecular tools is to identify biomarkers that could be used to further characterize each patient’s unique disease features and to predict how certain treatment modalities will affect patient survival and prognosis. The interplay between these biomarkers and molecular pathways involved in treatment response with disease progression and aggressiveness is a complex phenomenon. In this review, we describe the current state of the literature in regard to biomarkers that show promise in the clinical setting to predict response to treatments such as chemotherapy, radiation, and surgery in locally advanced and metastatic TNBC. Full article

Organoid culture is an emerging and promising 3D culture system by which three-dimensional cell aggregates have been produced from different organs and tissues. This new innovative culture technology preserves parental gene expression, as well as the biological features of parental cells in vitro and ensures maintenance of three-dimensional cell culture for prolonged periods, opening new encouraged scientific scenarios and making them a functioning and valid system for testing new drugs for tissue engineering studies and precision oncology medicine. Various research focused on organoids has been performed in perfusion bioreactors, an advanced device able to mimic the tumor environment, providing a physiological growth state and a long-term culture viability. Perfusion bioreactors have been used for the maintenance and growth of organoids as well as for tumor patient samples improving proliferation while supporting the development of extracellular matrix (ECM). The ability to mimic the tumor environment and to maintain patient-derived biopsies for a long time makes perfusion bioreactors an essential model for preclinical testing. Full article

Peritoneal carcinomatosis is a common presentation found in advanced-stage gastrointestinal (GI) and gynecological cancers. Combined cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant survival benefits for select patients. CRS/HIPEC is not currently provided in Newfoundland and Labrador (NL). The Canadian HIPEC Collaborative Group recommends that centres complete a minimum of one case monthly to maintain competency and achieve good outcomes. Thus, we aimed to demonstrate that the annual patient volume in NL justifies the feasibility of implementing a combined surgical and gynecological oncology CRS/HIPEC program. Methods: A retrospective chart review of the NL Cancer Care Registry identified patients with stage IV colorectal, appendiceal, or gastric cancer and stage III to IV epithelial ovarian cancer over a 1-year period (1 January 2020–31 December 2020) to identify the number of patients meeting the criteria for CRS/HIPEC and/or those referred out of province to receive the treatment. The results are presented as proportions and percentages. Results: Thirty-one patients were eligible to receive CRS/HIPEC during the study period (11 GI, 20 gynecological). Of the GI patients, 63% were referred out of province for the procedure. Gynecological patients underwent CRS and systemic therapy +/− outpatient intraperitoneal chemotherapy in NL. Conclusions: Allowing patients to receive this standard of care treatment near home reduces financial, social, and emotional stressors. Our results confirm a sufficient patient volume to support a combined CRS/HIPEC program in NL. The implementation of this program will require multidisciplinary collaboration, specialized training, equipment, and protocol development. Full article

Background: Few studies have compared the risk of reoperation by timing in breast reconstruction surgery after mastectomy. We evaluated the first and total number of reoperations by reconstruction timing in women with breast cancer undergoing primary mastectomy. Methods: A cohort study of 23,301 primary mastectomies in women with breast cancer undergoing either immediate breast reconstruction (IBR) or delayed reconstruction was carried out within Kaiser Permanente between 2010 and 2022. The first reoperation rate was calculated using cause-specific Cox Proportional Hazards Models, while Multiplicative Cox Proportional Hazards Models were used to account for mortality and timing in reoperation. Patients were continuously monitored for death, outcome of interest, loss to follow-up through healthcare membership termination, or study end date (31 December 2022). Results: In total, 78.4% (n = 18,276) of the cohort underwent IBR. The average follow-up time was 5.9 years (±3.8). The following covariates were imbalanced (standardized mean difference [SMD] ≥ 0.20) between IBR and delayed groups: BMI, smoking status, year of mastectomy, bilateral procedures, and reconstruction type. The crude incidence of first reoperation was 33.04% vs. 31.72% in IBR vs. delayed patients and the risk of reoperation was 18% higher in IBR patients (HR = 1.18, 95% CI = 1.12–1.25). There was no difference in the risk of reoperation by timing (p > 0.05) when assessing multiple reoperations. The reoperation risk was the highest for IBR patients who did not complete reconstruction or single-stage reconstruction. In addition, the first reoperation rate of IBR patients was higher in those who underwent expander–implant-based reconstruction. Conclusions: The first reoperation rate was higher in IBR patients compared to those who delayed reconstruction, although we failed to detect a difference for multiple returns to surgery, except in certain subgroups. Assessing reoperation risk by timing among different reconstruction modalities can aid patients in making informed decisions about the type of breast reconstruction to undergo. Full article

This paper reviews the surgical management of peritoneal carcinomatosis as new surgical methods have been developed within the past few decades. Traditional methods included cytoreductive surgery with hyperthermic intraperitoneal chemotherapy; however, a new method has been developed, Pressurized Intraperitoneal Aerosol Chemotherapy. This method is minimally invasive while allowing for promising outcomes in those who have exhausted therapy options or require palliative therapy. The goal of this paper is to compare and contrast the traditional and standard method with the newer method for intraoperative delivery of chemotherapy. Full article

Bladder cancer, a highly heterogeneous disease, necessitates precise diagnostic and therapeutic strategies to enhance patient outcomes. Metabolomics, through comprehensive small-molecule analysis, provides valuable insights into cancer-associated metabolic alterations at the cellular, tissue, and systemic levels. Concurrently, molecular imaging modalities like PET, MRI, and CT enable the non-invasive, real-time visualization of tumor biology, facilitating the spatial and functional assessment of biomarkers. Key findings highlight the identification of metabolomic profiles correlated with cancer progression, recurrence, and treatment responses across serum, urine, and tissue samples. Advanced analytical platforms, such as LC-MS and NMR, uncover distinct metabolic signatures and pathway alterations in glycolysis, amino acid metabolism, and lipid biosynthesis. Molecular imaging further enhances staging accuracy and treatment monitoring by visualizing metabolic activity and receptor expression. The integration of these technologies addresses the limitations of invasive diagnostic methods and paves the way for precision oncology. Future advancements should focus on multi-omics integration, AI-driven analysis, and large-scale clinical validation to ensure broad accessibility and transformative impacts on bladder cancer management. Full article