Present and Future of Personalized Medicine in Adult Genitourinary Tumors

Ciccarese, Chiara; Santoni, Matteo; Massari, Francesco; Liu, Cheng; López-Beltrán, Antonio; Scarpelli, Marina; Conti, Alessandro; Cascinu, Stefano; Montironi, Rodolfo

doi:10.2217/fon.15.30

Cited by 11 publications

(6 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The future vision for PM aims to include integrated ‘omics’ data which may reveal insights into tumour biology through study not only of genomics but also transcriptomics, proteomics, metabolomics, immune pathways and the microbiome. Our increasing understanding of these cellular pathways and their mechanistic links to the pathogenesis of cancer has led to the creation of many targeted systemic agents for a variety of cancers, including GU cancers 38,39 …”

Section: Precision Medicine and Its Potential Benefits In Alleviating...mentioning

confidence: 99%

The potential role of precision medicine to alleviate racial disparities in prostate, bladder and renal urological cancer care

Sindhu,

Dovey,

Thompson

et al. 2024

BJUI Compass

View full text Add to dashboard Cite

BackgroundRacial disparities in oncological outcomes resulting from differences in social determinants of health (SDOH) and tumour biology are well described in prostate cancer (PCa) but similar inequities exist in bladder (BCa) and renal cancers (RCCs). Precision medicine (PM) aims to provide personalized treatment based on individual patient characteristics and has the potential to reduce these inequities in GU cancers.ObjectiveThis article aims to review the current evidence outlining racial disparities in GU cancers and explore studies demonstrating improved oncological outcomes when PM is applied to racially diverse patient populations.Evidence acquisitionEvidence was obtained from Pubmed and Web of Science using keywords prostate, bladder and renal cancer, racial disparity and precision medicine. Because limited studies were found, preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines were not applied but rather related articles were studied to explore existing debates, identify the current status and speculate on future applications.ResultsEvidence suggests addressing SDOH for PCa can reverse racial inequities in oncological outcomes but differences in incidence remain. Similar disparities in BCa and RCC are seen, and it would be reasonable to suggest achieving parity in SDOH for all races would do the same. Research applying a PM approach to different ethnicities is lacking although in African Americans (AAs) with metastatic castrate‐resistant prostate cancer (mCRPCa) better outcomes have been shown with androgen receptor inhibitors, radium‐223 and sipuleucel. Exploiting the abscopal effect with targeted radiation therapy (RT) and immunotherapy has promise but requires further study, as does defining actionable mutations in specific patient groups to tailor treatments as appropriate.ConclusionFor all GU cancers, the historical underrepresentation of ethnic minorities in clinical trials still exists and there is an urgent need for recruitment strategies to address this. PM is a promising development with the potential to reduce inequities in GU cancers, however, both improved understanding of race‐specific tumour biology, and enhanced recruitment of minority populations into clinical trials are required. Without this, the benefits of PM will be limited.

show abstract

Section: Precision Medicine and Its Potential Benefits In Alleviating...mentioning

confidence: 99%

The potential role of precision medicine to alleviate racial disparities in prostate, bladder and renal urological cancer care

Sindhu,

Dovey,

Thompson

et al. 2024

BJUI Compass

View full text Add to dashboard Cite

show abstract

“…Based on this evidence, assessing the expression of PD-1/PD-L1 or other emerging immunotargets only at the diagnosis of metastatic disease may not reflect tumour dynamicity. To improve the feasibility and reduce the clinical impact of re-biopsy, assessing biomarkers on circulating tumour cells (CTCs) or exosomes [ 37 ] may represent a noninvasive strategy that can be performed several times during cancer therapy to reflect changes that occurred in the tumour environment. The early identification of validated biomarkers will be crucial to definitively carry immunotherapy into the era of precision medicine and to optimize the cost-effectiveness of these agents in cancer patients [ 38 , 39 ].…”

Section: Future Challengesmentioning

confidence: 99%

Immunotherapy in renal cell carcinoma: latest evidence and clinical implications

Santoni

Massari

Nunno

et al. 2018

DIC

Self Cite

View full text Add to dashboard Cite

Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC). The optimal combination between immunotherapy and targeted agents (as well as the possible favourable sequential therapy of these two classes of drugs) remains an open question at this moment. Several trials are currently underway to assess the combination of anti-programmed-death 1 (PD-1) or anti-PD-ligand(L)1 agents with other immunotherapies or with anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). In this editorial, we described the results of the most recent clinical trials on the use of immunotherapies in RCC and the emerging data on the research for reliable biomarkers of tumour response in this setting. In addition, we have focused on the role of the gut microbiome and tumour microenvironment in the development of future therapeutic strategies for RCC patients.

show abstract

“…To improve the feasibility and reduce the clinical impact of re-biopsy, assessing biomarkers on circulating tumor cells (CTCs) or exosomes ( 111 ) may represent a not invasive strategy that can be performed several times during cancer therapy in order to reflect the changes occurred in the tumor environment. An early identification of validated biomarkers would be crucial to definitively place immunotherapy into the era of precision medicine and to optimize the cost-effectiveness of ICI agents in cancer patients ( 50 , 112 ).…”

Section: Future Perspectivementioning

confidence: 99%

The Identification of Immunological Biomarkers in Kidney Cancers

et al. 2018

Self Cite

View full text Add to dashboard Cite

The recent approval of several agents have revolutionized the scenario of therapeutic management of metastatic renal cell carcinoma (RCC) allowing us to reach important clinical end points with extended patients' survival. Actually, every new drug approved has represented an important step forward to the improvement of patient's survival. On the other hand, we now understand that RCC includes a large group of tumor entities, each of them with different genetic and mutational alterations, but also showing different clinical behavior; a reason behind the needs of subtype specific personalized approach to therapy of RCC. Immunotherapy is gradually becoming a key factor in the therapeutic algorithm for patients with locally advanced or metastatic RCC. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors (ICI), gathering prognostic and predictive information about FDA-indicated tumors seems to be prudent. Robust and reliable biomarkers are crucial for patient's selection of treatments with immunomodulatory drugs. PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including RCC. Each FDA approved PD-1/PD-L1 drug is paired with a PD-L1 Immunohistochemistry (IHC) assay. Thus, there is need for improved knowledge and application of PD-1/PD-L1 IHC biomarkers in daily practice. IHC staining appears in membranous fashion. The atezolizumab approved IHC assay is unique in that only immune cell staining is quantified for the use of this assay in RCC. A single biomarker for patient selection may not be feasible, given that immune responses are dynamic and evolve over time. Biomarker development for ICI drugs will likely require integration of multiple biologic components like PD-L1 expression, TILs and mutational load. New methodological approaches based on digital pathology may be relevant since they will allow recognition of the biomarker and to objectively quantitate its expression, and therefore might produce objective and reproducible cut-off assessment. Multidisciplinary approach is very much needed to fully develop the current and future value of ICI in clinical practice.

show abstract

Present and Future of Personalized Medicine in Adult Genitourinary Tumors

Cited by 11 publications

References 57 publications

The potential role of precision medicine to alleviate racial disparities in prostate, bladder and renal urological cancer care

The potential role of precision medicine to alleviate racial disparities in prostate, bladder and renal urological cancer care

Immunotherapy in renal cell carcinoma: latest evidence and clinical implications

The Identification of Immunological Biomarkers in Kidney Cancers

Contact Info

Product

Resources

About