Cancers最新文献

Background/objectives: Prostate cancer (PCa) is the second leading cause of cancer-related death in men. The increase in incidence rates of more advanced and aggressive forms of the disease year-to-year fuels urgency to find new therapeutic interventions and bolster already established ones. PCa is a uniquely targetable disease in that it is fueled by male hormones (androgens) that drive tumorigenesis via the androgen receptor or AR. Current standard-of-care therapies directly target AR and its aberrant signaling axis but resistance to these therapies commonly arises, and the mechanisms behind the onset of therapy-resistance are still elusive. Research has shown that even with resistant disease, AR remains the main driver of growth and survival of PCa, and AR target genes and cofactors may help mediate resistance to therapy. Here, we focused on a homeobox transcription factor that exhibits a close relationship with AR-NKX3.1. Though NKX3.1 is traditionally thought of as a tumor suppressor, it has been previously reported to promote cancer cell survival by cooperating with AR. The role of NKX3.1 as a tumor suppressor perhaps in early-stage disease also contradicts its profile as a diagnostic biomarker for advanced prostate cancer.

Methods: We investigated the physical interaction between NKX3.1 and AR, a modulated NKX3.1 expression in prostate cancer cells via overexpression and knockdown and assayed subsequent viability and downstream target gene expression.

Results: We find that the expression of NKX3.1 is maintained in advanced PCa, and it is often elevated because of aberrant AR activity. Transient knockdown experiments across various PCa cell line models reveal NKX3.1 expression is necessary for survival. Similarly, stable overexpression of NKX3.1 in PCa cell lines reveals an androgen insensitive phenotype, suggesting NKX3.1 is sufficient to promote growth in the absence of an AR ligand.

Conclusions: Our work provides new insight into NKX3.1's oncogenic influence on PCa and the molecular interplay of these transcription factors in models of late-stage prostate cancer.

Background/objectives: Breast cancer survivors undergoing long-term endocrine therapy often experience multiple symptoms, including pain, fatigue, sleep disturbance, hot flashes, anxiety, and depression. This study explored the feasibility and acceptability of integrating acupuncture for symptom management in medically underserved breast cancer survivors.

Methods: This randomized controlled trial was conducted at two clinics serving medically underserved populations. Breast cancer survivors (N = 62) were randomized to receive acupuncture (n = 31) or usual care (n = 31). The acupuncture group underwent 10 sessions over 5 weeks. Symptoms were assessed at baseline and Weeks 6 and 12.

Results: The majority of participants (55%) were Black, mean age was 55.2 ± 9.3 years, and 62.9% had a household income below $55,000. Retention (90.3%), engagement (93.1%), and acceptability (92.8%) rates were high, demonstrating that integrating acupuncture into care for medically underserved breast cancer survivors is both feasible and acceptable. At Week 6, the acupuncture group showed significant reduction compared to the usual care group in pain, fatigue, sleep disturbance, depression, anxiety, and the symptom cluster score. All improvements persisted to Week 12 except for those in anxiety.

Conclusions: Integrating acupuncture for symptom management in medically underserved breast cancer survivors is both feasible and acceptable. This approach offers potential benefits for reducing multiple symptoms and addressing health disparities.

Background/Objectives: Liquid biopsy methods have gained prominence as minimally invasive tools to improve cancer treatment outcomes. Circulating tumor cells (CTCs) offer valuable insights into both primary and metastatic lesions. However, validating the CTC test results requires confirmation that the detected cells originate from cancer tissue. While studies have identified CTCs in colorectal cancer (CRC) patients using molecular markers, simultaneous validation of their cancer tissue origin remains unexplored. Methods: This study introduces a simple approach to detect adenomatous polyposis coli (APC) gene abnormalities alongside established CTC markers using a molecular imaging flow cytometer (MI-FCM). Given that APC gene abnormalities occur in 60-70% of CRC patients, their detection serves as strong evidence of cancer origin. Results: Our method achieved 92% concordance with DNA sequence analysis of tumor-derived cells. In a proof-of-concept study using 5 mL of whole blood from CRC patients, we observed a high frequency of cells exhibiting APC abnormalities, cytokeratin (CK), and vimentin (Vim) expression. Extending the study to 80 CRC patients across pathological stages I-IV confirmed CK and Vim as valid CTC markers. Three distinct cell populations were identified in blood: CK+/Vim-, CK+/Vim+, and CK-/Vim+. CTC number and frequency increased progressively with cancer stage. Conclusions: This is the first report demonstrating CK and Vim as effective markers for direct CTC detection in CRC patients. Our findings provide evidence-based validation of CTC markers, offering new insights and advancing approaches for patient care.

Background: Historically, the standard of care for advanced biliary tract cancers (aBTCs) was gemcitabine plus cisplatin (GemCis). Immunotherapy plus GemCis is now recommended as a first-line treatment for aBTCs. Whether patients can tolerate eight cycles of GemCis in clinical practice, as per the Advanced Biliary Cancer (ABC)-02 study, remains to be assessed. We performed a retrospective observational cohort study to assess real-world treatment patterns and overall survival (OS) in patients with de novo or recurrent aBTCs treated with first-line gemcitabine-based chemotherapy in the United States. Methods: This retrospective observational cohort study used Optum's de-identified Market Clarity Data (Market Clarity). Adults diagnosed with de novo or recurrent aBTCs in the United States who began first-line gemcitabine-based chemotherapy from January 2016-March 2022 were identified and followed from index until death, the end of continuous enrolment, or the end of study period. Treatment patterns and OS were assessed. Results: Overall, 559 patients were included (de novo, n = 462; recurrent, n = 97). GemCis was the most common first-line therapy received (de novo: 73.8%; recurrent: 57.7%). Most patients received approximately five cycles of GemCis; median (95% CI) time to discontinuation was 4.6 (4.3-5.1) months. Most patients died over the follow-up period (de novo: 70.3%; recurrent: 62.9%). Median OS (95% CI) was 14.2 (12.1-16.1) months (de novo) and 18.5 (15.6-26.9) months (recurrent). Conclusions: GemCis was the most common first-line therapy received during the study period; most patients were unable to receive eight cycles of GemCis. Survival was limited over the follow-up period, highlighting the need for new treatments for aBTCs. Future studies are warranted to understand the real-world impact of first-line immunotherapy plus GemCis for patients with aBTCs.

Background/objectives: Robot-assisted and open radical prostatectomy (RARP and ORP) are established procedures for localized prostate cancer, with comparable oncological and functional outcomes. Little is known about patients' knowledge of both procedures. This study aimed to examine comparatively the informational behaviour and knowledge of patients undergoing ORP vs. RARP.

Methods: This prospective, multicentre study included patients who underwent RARP or ORP prior to presurgery counselling. The questionnaires gathered information about patients' information-seeking behaviours and their assessment of outcomes for RARP vs. ORP. We investigated risk factors for the misperception of procedure outcomes.

Results: A total of 508 patients were included (307 RARP (60%); 201 ORP (40%)). The most common sources of information were outpatient urologists (84%), urologic departments (67%) and the internet (57%). Compared with ORP, RARP patients more often received the same amount of information about both procedures (60% vs. 40%, p < 0.001). Compared with ORP, RARP patients wrongfully considered their procedure to be superior in terms of oncological and functional outcomes. In the multivariable analysis, age > 66 years (OR 2.1, p = 0.02), no high school degree (OR 1.9, p = 0.04), unbalanced information search (OR 2.4, p = 0.02), RARP patient status (OR 8.9, p < 0.001), and treatment at a centre offering only one procedure (OR 3.5, p < 0.001) were independent predictors of misperception.

Conclusions: RARP patients wrongfully considered their intervention to be oncologically and functionally more beneficial than ORP patients perceived it to be. This may be due to unbalanced sources of information. Urologists and surgical centres must address this misperception to enable patients to make informed decisions.

Background/Objectives: Desmoid-type fibromatosis (DTF) is a locally invasive tumor composed of myofibroblast-like cells and collagen; it does not metastasize but can cause significant local morbidity. Most sporadic cases are associated with mutations in the CTNNB1 gene, which encodes beta-catenin. Various treatments have been used with differing efficacy and toxicity profiles. At our institution, pegylated liposomal doxorubicin (PLD) has become the preferred treatment for patients with DTF. We aim to describe our experience using PLD in patients with DTF who require treatment. Methods: A retrospective review of 61 DTF patients (41 females, 20 males) treated between 2000 and 2023 was conducted to assess the efficacy and toxicity of PLD. Results: Of the 26 patients treated with PLD, 23 had follow-up clinical data to assess benefit. Twenty-one showed clinical benefit, and only one progressed. Two patients did not benefit from PLD due to infusion reactions and chose alternative therapies. The primary side effect of PLD was hand-foot syndrome (HFS), but dose reduction and extended intervals allowed most patients to tolerate treatment. Other treatments, such as methotrexate, vinblastine/vinorelbine, and sorafenib, also showed activity but had significant toxicities, including severe HFS, malaise, and hypertension. Interestingly, 31 out of 61 patients had a pre-existing history of psychiatric conditions (primarily depression and anxiety), and 6 of 41 women had personal or family history of polycystic ovary syndrome (PCOS). Additionally, 15 patients had obesity, and 4 had hypothyroidism. Conclusions: PLD is an effective and well-tolerated treatment for DTF, with good clinical responses at lower, tolerable doses. The association of pre-existing psychiatric diagnoses, PCOS, and obesity warrants further investigation.

Background/Objectives: Inadequate dosing and respiratory motion contribute to local recurrence for oligometastatic disease (OMD). While short-term LC rates are well-documented, data on long-term LC remain limited. This study investigated long-term LC after stereotactic body radiotherapy (SBRT), using respiratory motion management techniques. Methods: This retrospective study took place at UZ Brussel with follow-up until Oct 2024. It analyzed oligometastatic patients treated with SBRT between Jul 2012 and Feb 2017. Treatment involved delivering 50 Gy in 10 fractions on the 80% isodose line, building on data from a prior prospective study. Lesion movement was managed using internal target volume (ITV) or dynamic tumor tracking (DTT) with marker. The primary endpoint of the study was long-term LC and identifying variables associated with it using a Cox proportional hazards model. Results: A total of 100 patients were treated for a total of 211 metastatic lesions. Lesions were predominantly in the lungs (74%) and treated using ITV (88%). LC rates at 1, 3, 5, and 10 years were 76.5%, 53.8%, 38.1%, and 36.3%, respectively. Improved LC was observed in locations other than lung and liver (HR: 0.309; p = 0.024) and with increasing age (HR: 0.975; p < 0.010). Worse LC was seen in liver lesions (HR: 1.808; p = 0.103) and systemic therapy post-radiotherapy (HR: 3.726; p < 0.001). No significant associations were found with tumor size or tumor motion, nor between the two motion management strategies used (DTT and ITV). Conclusions: Appropriate motion management is key in LC for OMD. No significant difference in LC was found between both techniques. Lesion location, patient age, and systemic therapy post-radiotherapy were prognostic factors for LC.

Background: Oral therapeutic options for plexiform neurofibromas (PNs) in individuals with neurofibromatosis type 1 (NF1) are receiving attention in clinical research. The MEK inhibitor (MEKi) Selumetinib is FDA-approved in children ages 2+ years with inoperable PNs, and shows activity in adults. Prolonged therapy with selumetinib is necessary to maintain tumor reduction. Therefore, investigating long-term adherence is vital to understand patterns of adherence over time and its impact on clinical outcomes. Mixed methods research offers rich information about adherence that can inform future intervention trials, and can assist practitioners in addressing medication adherence concerns.

Methods: This mixed-method pilot study is the first examination of the feasibility of a technology-based adherence assessment method, the medication events monitoring system (MEMS^TM), among individuals with NF1-PN. Adherence was monitored in a small sample of patients (N = 12; mean age = 34.36 years; 58% male) with NF1 and PN across eighteen 28-day treatment cycles. Qualitative data were obtained from individual interviews using inductive and deductive techniques for thematic analysis.

Results: The predetermined criterion was met, suggesting that using MEMS^TM is feasible despite some challenges with the caps. Depression and overall stress were significantly related to reduced adherence, although these results should be considered hypothesis-generating. Barriers to medication adherence included forgetting and the timing of doses related to eating. Facilitators included consistency, reminders, and social support.

Conclusions: This study highlights patient characteristics that may be related to increased risk for nonadherence, as well as challenges with electronic pill caps that should be considered in future clinical trials for NF1-related PN. Results can inform future adherence interventions for adults with NF1 and PNs. Future research with larger samples is needed to fully explore factors related to long-term medication adherence among individuals with NF1.

Chimeric antigen receptor T-cell (or CAR-T) therapy and bispecific antibodies (BsAbs) have revolutionized the treatment of hematologic malignancies, offering new options for relapsed or refractory cases. However, these therapies carry risks of early complications, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and delayed issues like graft-versus-host disease (GVHD), infections, and secondary cancers. Effective management requires early diagnosis using advanced biomarkers and imaging, along with prompt interventions involving immunosuppressants, corticosteroids, and cytokine inhibitors. A multidisciplinary approach is essential, integrating hematologists, oncologists, and infectious disease specialists, with emerging strategies like targeted biologics and personalized medicine showing promise in balancing efficacy with toxicity management. Ongoing research is critical to refine diagnostics and treatments, ensuring that these therapies not only extend survival but also improve patients' quality of life. This review provides critical insights for healthcare professionals to quickly recognize and treat complications of CAR-T and BsAbs therapies. By focusing on early detection through biomarkers and imaging and outlining timely therapeutic interventions, it aims to equip the multidisciplinary care team with the knowledge necessary to manage the challenges of these advanced treatments effectively, ultimately optimizing patient outcomes.

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β synthesized and secreted by immune cells. Herein, we discuss the importance of IL-1β derived from cancer cells which impacts primary tumors, particularly metastatic lesions, separately from and in addition to its more recognized role in immune-mediated inflammatory events. To this end, we focus on the instrumental contribution of IL-1β in the establishment and progression of advanced prostate adenocarcinoma. Special emphasis is placed on the potential role that the standard-of-care treatment strategies for prostate cancer patients have in unleashing IL-1β expression and production at metastatic sites. We conclude by reviewing the therapeutics currently used for blocking IL-1β signaling and propose a rationale for their concomitant use with standard-of-care treatments to improve the clinical outcomes of advanced prostate cancer.