Kidney transplantation is the optimal treatment for end-stage kidney failure. However, after successful kidney transplantation, patients require long-term immunosuppression. Due to immunosuppressive therapy, the development of malignancies is more common in solid organ transplant recipients than in the general population. Because renal transplantation has been performed for many decades—much longer than other solid organ transplants—data on malignancies in kidney allograft recipients are the most comprehensive. Malignancies are the third most common cause of death in kidney allograft recipients, after cardiovascular disease and infections. In kidney allograft recipients, malignancies may develop de novo, be transmitted with the transplanted organ, or arise from previously present but undiagnosed cancers in the recipient. Over 90% of malignancies in renal allograft recipients are de novo. In this review, we first present the epidemiology of malignancies after kidney transplantation. Subsequently, the most common urinary tract malignancies, along with their diagnosis, treatment, and screening, are discussed. We also outline the limitations of the published data, propose research priorities, and identify existing gaps and unmet needs.

Background/Objectives: In recent years, growing evidence that the tumor microenvironment (TME) plays crucial roles in the progression and treatment responses of various cancers has emerged. Unfortunately, we still do not fully understand the mechanisms through which the TME influences cancer development. Therefore, the aim of this study is to assess the impact of the TME on the clinical course of the disease, comparing primary and metastatic tumors. Materials and Methods: This retrospective study included 30 colorectal cancer patients for which tissue samples from primary and metastatic tumors were available for immunohistochemistry. A multiple Cox proportional hazards regression analysis was performed to characterize differences between the microenvironments of primary and metastatic tumors, as well as between lesions diagnosed at different times after resection. Results: Immune cell infiltration was higher in metastatic than primary tumors. Statistically significant differences were observed only in the central part of the tumor, while cell infiltration at the periphery had no prognostic significance. In the multivariate analysis, a positive correlation was revealed between the expression of Programmed Death-Ligand 1 (PD-L1) on primary tumor cells (TCs) and survival (HR: 5.43; 95% CI: 1.89-15.61; p = 0.0017). Conclusions: Primary and metastatic tumors differ regarding their tumor microenvironment. As such, the tumor immune status should be considered as a key factor when selecting a therapeutic strategy, as well as for post-treatment surveillance.

Introduction:Discrepancies between preclinical tests and clinical results raise serious concerns about the appropriateness of the current methodologies. In particular, cell biology approaches neglect fundamental physical parameters despite their relevance to in vivo conditions. Oxygen availability is critical for cell reactions; thus, the lack of consideration of hypoxia as the main regulator of the tumor microenvironment (TME) leads to misinterpreted data with consequences for translational applications. In this study, we show that mitomycin C (MMC), an antineoplastic antibiotic, is rarely used in ovarian cancer (OC) treatment despite its potential efficacy; we use MMC as an example of a treatment that warrants reevaluation under microenvironmental conditions, particularly during in vitro testing. Methods:To evaluate the effects of MMC and oxygen tension (pO2) on OC cells (SKOV3), HTA 2.0 microarrays were used, which demonstrated that hypoxia and MMC induced transcriptomic changes in OC cells. Their combination particularly emphasized the effect of pO2 modification on MMC activity. The most significant findings were verified in three other OC cell lines, namely, TOV112D, ES-2, and A2780. Results:Under normoxic conditions, MMC mostly affected several pathways associated with ribosome-related processes, whereas under hypoxic conditions, it induced modifications in the extracellular matrix (ECM). The most significantly upregulated gene in response to hypoxia-MMC treatment was MMP1, regulated by both MMC and hypoxia. Low pO2 levels during MMC treatment allowed the identification of important regulators, such as SPP1, and the corresponding processes, including cholesterol biosynthesis. Conclusion:Hypoxia modulated the effects of MMC on OC cells and identified genes that may serve as promising targets to enhance the effectiveness of MMC treatment.

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Background/Objectives: Chemotherapy is an aggressive form of oncological treatment often accompanied by numerous adverse effects. A patient's baseline status significantly influences the course of therapy, its efficacy, quality of life, and overall survival. This review aims to analyze the published peer-reviewed studies in this area and to assess whether they permit the formulation of preliminary recommendations for future prehabilitation protocols. Methods: An integrative review was conducted due to the limited number of relevant studies. Four databases-MEDLINE/PubMed (Medical Literature Analysis and Retrieval System Online/National Library of Medicine), Scopus, Cochrane, and Web of Science-were systematically searched for English-language articles published between 2010 and 13 January 2025, using the terms "prehabilitation," "chemotherapy," "drug therapy," and "neoadjuvant." A total of 162 records were retrieved. After duplicate removal, titles and abstracts were screened. The remaining papers were subjected to detailed analysis, resulting in ten studies with diverse methodologies being included. Results: We reviewed ten (n = 10) studies, most of which were reviews focused on breast cancer, indicating variation in the state of knowledge across different cancer types. A protein intake of 1.4 g/kg body mass helps preserve fat-free mass, with whey being more effective than casein. Supplementing EPA at a dose of 2.2 g/day may help prevent chemotherapy-related neurotoxicity and support appetite and weight maintenance. Physical activity, especially when it includes strength training, improves VO2max, preserves fat-free mass, and may reduce stress and anxiety. We identified one randomized controlled trial in which a single exercise session before the first dose of doxorubicin resulted in a smaller reduction in cardiac function. Continuous psychological support should be available. A combined behavioural and pharmacological approach appears to be the most effective strategy for smoking cessation. Conclusions: No official guidelines exist for prehabilitation before chemotherapy, and the availability of studies on this topic is very limited. The pre-treatment period represents a critical window for interventions. Further research is needed to evaluate the effectiveness and applicability of particularly single-component interventions.

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC.

Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic–therapeutic interventions. In this study, we validated the expression of six genes (MIR205HG, KRT5, KRT6A, KRT6C, SERPINB5, and DSG3), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C. Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

The number of patients with end-stage renal disease requiring hemodialysis and diagnosed with various types of cancer is constantly growing, but guidelines on systemic treatment in this particular clinical scenario are lacking. Testicular cancer is a highly curable malignancy, but data on post-orchidectomy systemic treatment based on cisplatin in patients requiring hemodialysis are scarce. We present two cases of patients with testicular germ cell tumors (one intermediate-risk seminoma and one low-risk non-seminoma) treated with chemotherapy while on hemodialysis in our center. Furthermore, we discuss the appropriate doses of cytotoxic drugs and the timing of hemodialysis.

2588 Background: CLN-619 is a human IgG1 antibody that prevents proteolytic cleavage of NKG2D ligands MICA/B from tumor cells, increasing tumor cell lysis by innate and adaptive immune cells. CLN-619 monotherapy demonstrated favorable safety and objective responses in multiple tumor types in a Ph1 study (ASCO 2023). Results from dose escalation in combination with P and updated results of monotherapy are reported. Methods: This first-in-human study (NCT05117476) enrolled pts ≥18y, ECOG 0/1 with advanced solid tumors to receive IV CLN-619 either as monotherapy or in combination with P (200 mg IV Q3W). CLN-619 was dosed at 1-10 mg/kg IV Q3W in the combo arm. Corticosteroid pre-medication is mandated before the first dose of CLN-619. Response (RECIST 1.1) is assessed every 9 wks. Results: As of 24 Nov 2023 data-cutoff (DCO), enrollment in both arms of the dose escalation was complete. The combination cohort enrolled 22 (18 evaluable) pts (median 66y, range 38-82; 50% female); pts had received median 3 prior therapies (range 1-7), 41% prior checkpoint inhibitor (CPI). No protocol defined DLTs were observed. Treatment-emergent adverse events (TEAEs) in ≥20% of pts were fatigue (36%), constipation (27%), and nausea (23%). Four patients (18%) experienced Grade (Gr) 1/2 infusion-related reactions. Two patients with NSCLC (1 EGFRm, 1 ALKrearr) had achieved confirmed partial response (PR). After DCO, 1 pt with gastric cancer improved from stable disease (SD) to PR at cycle 7 (pending confirmation). The monotherapy cohort enrolled 42 pts (median 61y, range 26-83; 60% female; median 3 prior (range 1-7); 52% prior CPI). No DLTs were observed. TEAEs in ≥20% of pts were infusion related reactions (26%), fatigue (24%), and abdominal pain (22%). One immune-related AE of maculopapular rash was reported but resolved with steroid taper and did not result in treatment discontinuation. Three previously reported confirmed responses in mucoepidermoid parotid (CR), serous endometrial (PR), and endometroid endometrial (PR) were durable through 13, 7, and 8 (ongoing) months, respectively. Nine pts achieved stable disease (SD) extending through ≥18 wks: 1 HR+ breast, 1 platinum-resistant ovarian, 2 cervical, 1 STK11+ adenocarcinoma lung, 1 uterine carcinosarcoma, 1 pancreatic, 1 salivary adenoid cystic carcinoma, 1 mediastinal intimal sarcoma. Clinical benefit rate at doses ≥1mg/kg (CR+PR+SD≥18 weeks) was 41% (12/29 evaluable pts). Conclusions: CLN-619 + P was well tolerated at doses ranging from 1 to 10 mg/kg. Objective responses were observed, including in tumor types typically unresponsive to P. Longer term follow-up for CLN-619 monotherapy confirms favorable safety and durable clinical benefit with extended treatment, including objective responses in multiple tumor types and pts progressing after CPI. Based on these findings, expansion cohorts will be opened in endometrial cancer and NSCLC. Clinical trial information: NCT05117476 .

There is a growing prevalence of pancreatic cancer, accompanied by accelerated disease progression and diminished survival rates. Radical resection with clear margins remains the sole viable option for achieving a long-term cure in patients. In cases of advanced, unresectable, and metastatic disease, chemotherapy based on leucovorin, 5-fluorouracil, irinotecan, oxaliplatin, gemcitabine, or nab-paclitaxel represents the cornerstone of the treatment. Considering the limited treatment options available following initial therapy, the strategy of repurposing commonly prescribed drugs such as antihypertensives into anti-cancer therapies in palliative treatment represents a promising avenue for enhancing survival in patients with pancreatic ductal adenocarcinoma. The repurposing of existing drugs is typically a more cost-effective and expedient strategy than the development of new ones. The potential for antihypertensive drugs to be employed as adjunctive therapies could facilitate a more comprehensive treatment approach by targeting multiple pathways involved in cancer progression and acquired resistance to treatment. Antihypertensive medications, particularly those belonging to the pharmacological classes of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers, are commonly prescribed and have well-established safety profiles, particularly among patients with pancreatic cancer who are affected by multiple comorbidities. Therefore, we emphasize the preclinical and clinical evidence supporting the use of antihypertensive agents in the treatment of pancreatic cancer, emphasizing their beneficial chemosensitizing effects.

Introduction:The aim of the study was to assess prognostic factors associated with an increased risk of recurrence of hepatocellular carcinoma (HCC) after radical treatment. Materials and methods:This is a retrospective, single-center analysis of data on HCC recurrence in patients who underwent radical treatment. Molecular tumor characteristics, baseline laboratory results and hepatic viral status were analyzed. Results:Data from 111 patients were included in the analysis. The most important prognostic factors for recurrence were vascular microinvasion (HR 4.54; 95 % CI 1.769-11.681; p 0.001), baseline white blood count (HR 2.13; 95 % CI 1.261-3.567; p 0.004) and baseline alpha-fetoprotein (HR 1.00009; 95 % CI 1.000001-1.00002; p 0.034). Microvascular invasion was only prognostic factor which correlate significantly with the overall survival (HR 5.04, 95 % CI 2.352-12.413; p < 0.001). PD-L1 expression was confirmed in 4 patients and all of them developed a disease recurrence. However, there was no statistically significant assosciation with prognosis. The presence of CD68 tumor-associated macrophages was confirmed in 62 patients, ranging from 5 % to 40 %. Analysis showed that CD68 was not associated with the risk of recurrence of HCC. Conclusions:The results confirm that microvascular invasion is the most important factor associated with an increased risk of hepatocellular carcinoma recurrence and death, while PD-L1 and CD68 expression did not have an impact on patient prognosis.

Hepatocellular carcinoma is one of the most common cancers worldwide. Despite progress in treatment, recurrence after radical treatment is common, and the prognosis remains poor for patients with advanced disease. Therefore, there is a need to identify prognostic and predictive factors for the response to therapy or more intensive surveillance or treatment. Because the tumor microenvironment plays a crucial role in the development of cancer and metastasis, it is a crucial need to understand processes that are involved in carcinogenesis. Within the microenvironment, several immune cells with different roles are present. One of the most important of these is tumor-associated macrophages. These cells may exert either antitumor or protumor roles. Several studies have suggested that tumor-associated macrophages can be used as prognostic markers. Furthermore, they may be involved in resistance to immunotherapy or systemic treatment. As they play an important role in cancer development, tumor-associated macrophages are also a good target for therapy. In this review, we briefly summarize recent progress on knowledge regarding the basic molecular characteristics, impact on prognosis and potential clinical implications of tumor-associated macrophages in hepatocellular carcinoma.

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of “mille-feuille sign”, so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p < 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p < 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively.

Introducing PARP inhibitors maintenance therapy into clinical practice significantly improved treatment outcomes in patients with high-grade platinum-sensitive advanced ovarian cancer, the most lethal gynecological malignancy. Niraparib is a potent PARP inhibitor whose safety and efficacy were assessed in the placebo-controlled, randomized clinical trial PRIMA. Niraparib significantly prolonged progression-free survival in the overall population of high-grade advanced ovarian cancer regardless of BRCA1 and BRCA2 mutation and homologous deficiency status compared to placebo. However, the most significant benefit was observed in BRCA mutated and homologous recombination deficient subgroups. Niraparib has a manageable toxicity profile and is well-tolerated by patients. Most common toxicities are hematological and can be managed with drug interruption and/or dose reduction that do not decrease efficacy. Niraparib is recommended for patients who responded to the first-line chemotherapy with platinum compound regardless of homologous recombination status. This review will discuss the use of niraparib in newly diagnosed advanced ovarian cancer patients focusing on its efficacy and tolerability. Additionally, a case series will be presented to further discuss this drug use in clinical practice in Poland.

Non-small cell lung cancer (NSCLC) encompasses distinct histopathological subtypes, namely adenocarcinoma (AC) and squamous cell lung carcinoma (SCC), which require precise differentiation for effective treatment strategies. In this study, we present a novel molecular diagnostic model that integrates tissue-specific expression profiles of microRNAs (miRNAs) obtained through next-generation sequencing (NGS) to discriminate between AC and SCC subtypes of NSCLC. This approach offers a more comprehensive and precise molecular characterization compared to conventional methods such as histopathology or immunohistochemistry. Firstly, we identified 31 miRNAs with significant differential expression between AC and SCC cases. Subsequently, we constructed a 17-miRNA signature through rigorous multistep analyses, including LASSO/elastic net regression. The signature includes both upregulated miRNAs (hsa-miR-326, hsa-miR-450a-5p, hsa-miR-1287-5p, hsa-miR-556-5p, hsa-miR-542-3p, hsa-miR-30b-5p, hsa-miR-4728-3p, hsa-miR-450a-1-3p, hsa-miR-375, hsa-miR-147b, hsa-miR-7705, and hsa-miR-653-3p) and downregulated miRNAs (hsa-miR-944, hsa-miR-205-5p, hsa-miR-205-3p, hsa-miR-149-5p, and hsa-miR-6510-3p). To assess the discriminative capability of the 17-miRNA signature, we performed receiver operating characteristic (ROC) curve analysis, which demonstrated an impressive area under the curve (AUC) value of 0.994. Our findings highlight the exceptional diagnostic performance of the miRNA signature as a stratifying biomarker for distinguishing between AC and SCC subtypes in lung cancer. The developed molecular diagnostic model holds promise for providing a more accurate and comprehensive molecular characterization of NSCLC, thereby guiding personalized treatment decisions and improving clinical management and prognosis for patients.