Publications by authors named "Marc A Dall'Era"
Neoadjuvant therapy (NAT) has been studied in clinically localized prostate cancer (PCa) to improve the outcomes from radical prostatectomy (RP) by 'debulking' of high-risk PCa; however, using androgen deprivation therapy (ADT) at this point risks castration resistant PCa (CRPC) clonal proliferation. Our goal is to identify alternative NAT that reduce hormone sensitive PCa (HSPC) without affecting androgen receptor (AR) transcriptional activity. PCa is associated with increased expression and activation of the epidermal growth factor receptor (EGFR) family, including HER2 and ErbB3.
View Article and Find Full Text PDFFunctional inversion of circadian regulator REV-ERBα leads to tumorigenic gene reprogramming.
Proc Natl Acad Sci U S A
October 2024
Article Synopsis
- Dysregulation of circadian rhythm (CR) is linked to cancer, with the study highlighting a major shift in the function of the CR regulator REV-ERBα in tumors.
- REV-ERBα transitions from a gene repressor in normal tissues to a gene activator in cancer, activating many tumor-related signaling pathways through its partnership with other proteins like FOXA1.
- Targeting REV-ERBα with the drug SR8278 can reduce its function and, when combined with BRD4 inhibitors, effectively suppress tumor growth by disrupting tumorigenic gene programs.
Objective: To assess the distribution of key mutations across tumour sizes in clear-cell renal cell carcinoma (ccRCC), and secondarily to examine the prognostic impact of aggressive mutations in smaller ccRCCs.
Patient And Methods: The distribution of mutations (VHL, PBRM1, SETD2, BAP1 and CDKN2A loss) across tumour sizes was assessed in 1039 ccRCCs treated with nephrectomy in cohorts obtained from the Tracking Cancer Evolution (TRACERx), The Cancer Genome Atlas (TCGA) and the Cancer Genomics of the Kidney (CAGEKID) projects. Logistic regression was used to model the presence of each mutation against size.
N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved "SELILKR" motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance.
View Article and Find Full Text PDFBackground: Treatment of patients with muscle-invasive bladder cancer (MIBC) includes cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Molecular subtypes have been associated with patient outcomes after NAC and RC, but the reported results have been highly inconsistent.
Objective: To evaluate the association of molecular subtypes from different classifiers with overall survival (OS) among patients with MIBC who underwent RC.
Article Synopsis
- Cisplatin-based neoadjuvant chemotherapy (NAC) is commonly used in muscle-invasive bladder cancer patients but can lead to renal toxicity, and radical cystectomy (RC) itself is a risk factor for renal injury.
- An analysis of 234 patients showed a significant decrease in estimated glomerular filtration rate (eGFR) after receiving NAC, with a 17% decline and an increase in chronic kidney disease stage ≥3 from 27% to 50% one year after surgery.
- In comparison, a control group that underwent RC without NAC had a smaller eGFR decline of 6% and a baseline higher incidence of stage ≥3 CKD, highlighting the renal risks associated with NAC prior to surgery
Background: Secondary malignancy is a long-term risk of radiation. External beam radiation therapy (EBRT) for prostate cancer treatment has been associated with later development of bladder cancer and worse bladder cancer features.
Objective: We sought to provide an updated comparison of the long-term risk of bladder cancer after different localized prostate cancer treatments.
Objective: Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), those with high risk disease have the greatest risk of recurrence and disease progression. The underutilization of intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) has been a longstanding concern in clinical practice. This study aimed to determine the disparities present in receipt of adjuvant intravesical chemotherapy and immunotherapy in treatment of patients with high grade NMIBC following initial transurethral resection of a bladder tumor (TURBT).
View Article and Find Full Text PDFArticle Synopsis
- Current research on renal cell carcinoma (RCC) indicates that data on tumor size and subtype, especially in relation to metastatic disease, is often based on limited studies, potentially overlooking those with metastases at diagnosis.
- The study utilized a large dataset from the Surveillance, Epidemiology and End Results registry to assess how tumor size and histologic subtype correlate with metastatic status in RCC patients diagnosed from 2004-2019.
- Findings revealed that larger tumor sizes correspond to higher rates of metastasis across various RCC subtypes, particularly for clear cell and papillary RCC, while chromophobe RCC showed lower rates even at larger sizes; this suggests previous reports may underestimate metastatic risks associated with tumor size.
Purpose: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort.
Materials And Methods: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy.
Purpose: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis).
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- Men with low-risk prostate cancer are increasingly choosing active surveillance (AS) instead of immediate treatment, but many later switch to active treatment.
- A multi-institutional study analyzed genetic data from over 5,000 prostate cancer patients who opted for AS to identify genetic factors that might predict those likely to switch to treatment.
- The study found 18 genetic variants related to the decision to change treatment and established a link between certain genetic risk scores and the likelihood of converting from AS to active treatment, suggesting that genetics could personalize monitoring and treatment decisions for these patients.
Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000.
View Article and Find Full Text PDFPurpose: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) in patients with nonmetastatic muscle-invasive bladder cancer (MIBC) confers an absolute survival benefit of 5%-10%. There is evidence that molecular differences between tumors may impact response to therapy, highlighting a need for clinically validated biomarkers to predict response to NAC.
Materials And Methods: Four bladder cancer cohorts were included.
Purpose: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.
Materials And Methods: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively.
Purpose: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC).
Materials And Methods: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles.
Objectives: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis.
Patients And Methods: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC.
Objective: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery.
Patients And Methods: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses.
Background: Emerging evidence has suggested that DNA repair gene alterations may be important in prostate cancer pathogenesis. In the current study, the authors sought to characterize alterations in DNA repair pathway genes in both primary and metastatic prostate tumors with attention to tissue distribution as well as specific genomic alterations.
Methods: The authors studied the distribution and type of alterations in 24 genes that are considered important for DNA repair in 944 prostate cancers harvested from localized and metastatic tumors.
Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC).
Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status.
Introduction: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC.
View Article and Find Full Text PDFThe purpose of this study was to evaluate the efficacy of radiofrequency ablation (RFA) of renal masses comparing a group who did not undergo intraprocedural CT and a group who did. A retrospective review included 45 consecutively registered patients who underwent RFA of renal masses. If an adequate biopsy specimen was not obtained or follow-up was inadequate, the patient was eliminated from review from calculation of primary technical efficacy.
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