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Mechanisms of Resistance in Genito-Urinary Cancers: Innovative Insights in Signaling and Therapeutic Targetings

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Special Issue Information
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Published Papers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 6913

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Special Issue Editor

Prof. Dr. Giuseppe Di Lorenzo

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Guest Editor

1. Medical oncology, AOU University Federico II, 80131 Napoli, Italy
2. Department of Medicine, University of Molise, 86100 Campobasso, Italy
Interests: prostate cancer; bladder cancer; kidney cancer; penile cancer; testicular cancer; genito-urinary cancers; chemotherapy; prognostic factors; biological agents; randomized trials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The management of metastatic genito-urinary cancers such as prostate, kidney, and urothelial cancers has dramatically changed in the last ten years.

New insights into the biology of cancer cells, mechanisms of neoangiogenesis, metastatization, cell death, and resistance have served as the foundation for new therapeutic targets that have modified the history of these cancers.

New androgen receptor signaling inhibitors (ARSI), tirosine kinase inhibitors (TKIs), immune check point inhibitors (CPIs), new chemotherapeutic agents (NCA) such as cabazitaxel, and fibroblastic growth factor (FGFR) inhibitors such as erdafitinib represent new therapies, effective options with overall survival, progression-free survival, and quality of life (QoL) improvement.

However, two questions are open today:

How to select the best drug among several available options considering the absence of predictive factors, elderly age, and clinical conditions of the patients. Preliminary findings have focused on circulating tumor cells (CTC) count and different clones of CTC as prognostic and predictive factors in prostate cancers;
How to overcome resistance to approved agents. PARP inhibitors and PSMA theranostics in prostate cancer, CPIs plus targeted therapy in kidney cancer, and FGFR inhibitors and CPIs with chemotherapy in selected subtypes of urothelial cancers show preliminary and interesting results. New treatments are also needed in penile and testicular cancers.

In this Special Issue, we will publish original research and reviews that provide new insights in genitourinary cancer, focusing on new mechanisms to overcome resistance to approved therapies and how it can be targeted therapeutically. New insights into AR mutation, the role of CTC, and new chemotherapeutic and immunotherapeutic agents will be particularly welcomed.

Prof. Dr. Giuseppe Di Lorenzo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

androgen receptors (AR)
ar-indipendent pathways
circulating tumors cells (CTC)
poli-adp riboso polimerase (PARP) inhibitors
new drugs
prostate specific membrane antigen (PSMA) theranostics
tyrosine kinases inhibitors (TKI)
immunotherapy
combined treatments in kidney cancers
fibroblastic growth factor receptor (FGFR) inhibitors

Published Papers (2 papers)

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Research

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15 pages, 1414 KiB

Open AccessArticle

Effect of Baseline Characteristics on Cabazitaxel Treatment Duration in Patients with Metastatic Castration-Resistant Prostate Cancer: A Post Hoc Analysis of the Compassionate Use/Expanded Access Programs and CAPRISTANA Registry

by Zafar Malik, Giuseppe Di Lorenzo, Angelika Pichler, Ugo De Giorgi, Simon Hitier, Evelyne Ecstein-Fraisse, Ayse Ozatilgan and Joan Carles

Cancers 2020, 12(4), 995; https://doi.org/10.3390/cancers12040995 - 17 Apr 2020

Cited by 2 | Viewed by 2554

Abstract

We examined factors that may impact cabazitaxel treatment duration in a real-life setting in a compassionate use program, expanded access program, and prospective observational study in metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC previously treated with docetaxel (N = 1621) received cabazitaxel 25 mg/m² intravenously every 3 weeks until disease progression, death, unacceptable toxicity or physician/patient decision. The median number of cabazitaxel cycles was six (range, 1–49); 708 patients (43.7%) received >6 cycles. Patients receiving >6 cycles tended to have a better Eastern Cooperative Oncology Group performance status of 0–1 (p = 0.0017 for ≤6 vs. >6 cycles). Overall, 348 patients (21.5%) were ≥75 years of age; 139 (39.9%) received >6 cycles. The main reason for discontinuation was disease progression; however, in patients receiving 1–2 cycles, the main reason for discontinuation was adverse events. Only 52 patients (3.2%) progressed during cycles 1–2. Cabazitaxel was well tolerated in these studies, which included some elderly and frail patients, offering clinicians an important treatment option in the management of mCRPC. Proactive management of adverse events may allow patients to receive a higher number of cabazitaxel cycles and derive greater benefit. Full article

(This article belongs to the Special Issue Mechanisms of Resistance in Genito-Urinary Cancers: Innovative Insights in Signaling and Therapeutic Targetings)

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Review

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14 pages, 4404 KiB

Open AccessFeature PaperReview

Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

by Carlo Buonerba, Pasquale Dolce, Simona Iaccarino, Luca Scafuri, Antonio Verde, Ferdinando Costabile, Martina Pagliuca, Rocco Morra, Vittorio Riccio, Dario Ribera, Pietro De Placido, Valeria Romeo, Felice Crocetto, Nicola Longo, Ciro Imbimbo, Sabino De Placido and Giuseppe Di Lorenzo

Cancers 2020, 12(2), 408; https://doi.org/10.3390/cancers12020408 - 10 Feb 2020

Cited by 33 | Viewed by 3958

Abstract

: Immunotherapy based on anti PD-1/PD-L1 inhibitors has proven to be more effective than sunitinib in the first-line setting of advanced renal cell carcinoma (RCC). RCC patients with sarcomatoid histology (sRCC) have a poor prognosis and limited therapeutic options. We performed a systematic review and a meta-analysis of randomized-controlled trials (RCTs) of first-line anti PD-1/PDL-1 agents vs. sunitinib, presenting efficacy data in the sub-group of sRCC patients. The systematic research was conducted on Google Scholar, Cochrane Library, PubMed and Embase and updated until 31th January, 2020. Abstracts from ESMO and ASCO (2010–2019) were also reviewed. Full texts and abstracts reporting about RCTs testing first-line anti-PD-1/ PD-L1 agents vs. sunitinib in RCC were included if sRCC sub-group analyses of either PFS (progression-free survival), OS (overall survival) or radiological response rate were available. Pooled data from 3814 RCC patients in the ITT (intention-to-treat) population and from 512 sRCC patients were included in the quantitative synthesis. In the sRCC sub-group vs. the ITT population, pooled estimates of the PFS-HRs were 0.57 (95%: 0.45–0.74) vs. 0.79 (95% CI: 0.70–0.89), respectively, with a statistically meaningful interaction favoring the sRCC sub-group (pooled ratio of the PFS-HRs = 0.64; 95% CI: 0.50–0.82; p < 0.001). Pooled estimates of the difference in CR-R (complete response-rate) achieved with anti-PD-1/PDL-1 agents vs. sunitinib were + 0.10 (95% CI: 0.04–0.16) vs. + 0.04 (95% CI: 0.00–0.07) in the sRCC vs. the non-sRCC sub groups, with a statistically meaningful difference of + 0.06 (95% CI: 0.02–0.10; p = 0.007) favoring the sRCC sub-group. Sarcomatoid histology may be associated with improved efficacy of anti PD-1/PDL-1 agents vs. sunitinib in terms of PFS and CR-R. Full article

(This article belongs to the Special Issue Mechanisms of Resistance in Genito-Urinary Cancers: Innovative Insights in Signaling and Therapeutic Targetings)

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