Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Iacovino, Maria Lucia; Miceli, Chiara Carmen; Felice, Marco De; Barone, Biagio; Pompella, Luca; Chiancone, Francesco; Zazzo, Erika Di; Tirino, Giuseppe; Corte, Carminia Maria Della; Imbimbo, Ciro; Vita, Ferdinando De; Crocetto, Felice

doi:10.3390/ijms23031133

Cited by 37 publications

(26 citation statements)

References 84 publications

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“…In general, TNBC, a kind of breast cancer that the absence of HR and HER2 receptor expression renders endocrine or anti-HER2 targeted therapy ineffective, can be divided into multiple subtypes by profiling gene expression [ 28 ]. Similar to other tumors, classification of molecular subtypes of TNBC paves the way for molecular-targeted drug development, which would provide more options for clinical treatment [ 28 , 29 ]. As a vital target for immunotherapy of various tumors, programmed cell death protein 1 (PD-1) and its ligand PD-L1 has a significant role in TNBC progression as well [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of platinum-based and non-platinum-based drugs on triple-negative breast cancer: meta-analysis

et al. 2022

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Background Triple-negative breast cancer (TNBC), the subtype of breast cancer with the highest mortality rate, shows clinical characteristics of high heterogeneity, aggressiveness, easy recurrence, and poor prognosis, which is due to lack of expression of estrogen, progesterone receptor and human epidermal growth factor receptor 2. Currently, neoadjuvant chemotherapy (NAT) is still the major clinical treatment for triple-negative breast cancer. Chemotherapy drugs can be divided into platinum and non-platinum according to the presence of metal platinum ions in the structure. However, which kind is more suitable for treating TNBC remains to be determined. Methods The relevant randomized clinical trials (RCTs) that explore the effectiveness of chemotherapy regimens containing platinum-based drugs (PB) or platinum-free drugs (PF) in treating TNBC patients were retrieved through PubMed, EMBASE, Cochrane Library, CNKI, and other literature platforms, above research findings, were included in the meta-analysis. The incidence of overall remission rate (ORR), pathological complete remission rate (pCR), overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and adverse events (AE) were compared between the two groups. Results In this study, 12 clinical trials with a total of 4580 patients were included in the analysis. First, the ORR in 4 RCTs was, PB vs PF = 52% vs 48% (RR = 1.05, 95% CI: 0.91–1.21, P = 0.48); the pCR in 5 RCTs was, PB vs PF = 48% vs 41% (RR = 1.38, 95% CI: 0.88–2.16, P = 0.17). CI: 0.88–2.16, P = 0.17; the other 2 RCTs reported significantly higher DFS and OS rates in the PB group compared with the PF group, with the combined risk ratio for DFS in the PB group RR = 0.22 (95% CI:0.06–0.82, P = 0.015); the combined risk ratio for DFS in the PF group RR = 0.15 (95% CI. 0.04–0.61, P = 0.008); OS rate: PB vs PF = 0.046 vs 0.003; secondly, 2 RCTs showed that for patients with BRCA-mutated TNBC, the pCR rate in the PB and PF groups was 18% vs 26%, 95% CI: 2.4–4.2 vs 4.1–5.1; meanwhile, the median subject in the PB group The median PFS was 3.1 months (95% CI: 2.4–4.2) in the PB group and 4.4 months (95% CI: 4.1–5.1) in the PC group; finally, the results of the clinical adverse effects analysis showed that platinum-containing chemotherapy regimens significantly increased the incidence of adverse effects such as thrombocytopenia and diarrhea compared with non-platinum regimens, while the incidence of adverse effects such as vomiting, nausea, and neutropenia was reduced. The incidence of adverse reactions was reduced. Conclusion Compared with non-platinum drugs, platinum drugs significantly improved clinical treatment effective indexes, such as PCR, ORR, PFS, DFS, and OS rate in the treatment of TNBC patients without BRCA mutant may cause more serious hematological adverse reactions. Accordingly, platinum-based chemotherapy should be provided for TNBC patients according to the patient's special details.

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Section: Discussionmentioning

confidence: 99%

Efficacy of platinum-based and non-platinum-based drugs on triple-negative breast cancer: meta-analysis

et al. 2022

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“…Immunotherapy has increasingly become an important part of the treatment of tumor therapy [ 26 , 27 ]. The sensitivity of immunotherapy for HCC directly determines the prognosis, which is very critical.…”

Section: Discussionmentioning

confidence: 99%

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Wang

Ding

et al. 2022

Eur J Med Res

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Background Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment. Methods The expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm. Results LPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC. Conclusions LPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma.

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“…Immunotherapies including immune-checkpoint inhibitors such as avelumab, approved for maintenance therapy by Health Canada in 2021 [ 12 ], and pembrolizumab, approved in the second-line setting [ 14 ], are now more widely integrated into clinical practice. Not all patients respond to immune-checkpoint inhibitors, and the identification of those patients who are more likely to respond is an important area of ongoing research [ 24 , 25 ]. During the period of this study, the absence of reimbursement for second-line immunotherapies may have contributed to the low rate of referrals to medical oncologists for those patients who were thought to be unfit for chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Understanding Treatment Patterns and Outcomes among Patients with De Novo Unresectable Locally Advanced or Metastatic Urothelial Cancer: A Population-Level Retrospective Analysis from Alberta, Canada

et al. 2022

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Despite a high disease burden, real-world data on treatment patterns in patients with unresectable locally advanced or metastatic urothelial carcinoma (la/mUC) in Canada are limited. This retrospective, longitudinal cohort study describes treatment patterns and survival in a population of patients with de novo unresectable la/mUC from Alberta, Canada, diagnosed between 1 January 2015 and 31 December 2019, followed until mid-2020. The outcomes of interest were systemic therapy treatment patterns and overall survival (OS). Of 206 patients, most (65.0%, n = 134) did not receive any systemic therapies. Of 72 patients (35.0%) who received first-line systemic therapy, the median duration of treatment was 2.8 months (IQR 3.3). Thirty-five patients (48.6% of those who received first-line therapy) received subsequent second-line therapy, for a median of 3.0 months (IQR 3.3). In all patients (n = 206), the median OS from diagnosis was 5.3 months (95% CI, 4.5–7.0). In patients who received treatment, the median OS from the initiation of first-line and second-line systemic therapy was 9.1 (6.4–11.6) and 4.6 months (3.9–19.2), respectively. The majority of patients did not receive first-line systemic therapy, and, in those who did, survival outcomes were poor. This study highlights the significant unmet need for safe and efficacious therapies for patients with la/mUC in Canada.

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Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Cited by 37 publications

References 84 publications

Efficacy of platinum-based and non-platinum-based drugs on triple-negative breast cancer: meta-analysis

Efficacy of platinum-based and non-platinum-based drugs on triple-negative breast cancer: meta-analysis

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Understanding Treatment Patterns and Outcomes among Patients with De Novo Unresectable Locally Advanced or Metastatic Urothelial Cancer: A Population-Level Retrospective Analysis from Alberta, Canada

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