Abstract
The development of new systemic agents has led us into a “golden era” of management of metastatic renal cell carcinoma (RCC). Certainly, the approval of immune-checkpoint inhibitors and the combination of these with targeted compounds has irreversibly changed clinical scenarios. A deeper knowledge of the molecular mechanisms that correlate with tumor development and progression has made this revolution possible. In this amazing era, novel challenges are awaiting us in the clinical management of metastatic RCC. Of these, the development of reliable criteria which are able to predict tumor response to treatment or primary and acquired resistance to systemic treatments still remain an unmet clinical need. Thanks to the availability of data provided by studies evaluating genomic assessments of the disease, this goal may no longer be out of reach. In this review, we summarize current knowledge about genomic alterations related to primary and secondary resistance to target therapy and immune-checkpoint inhibitors in RCC.
Highlights
Renal cell carcinoma (RCC) represents 5% of all cancers in men and 3% in women
In a study of four patients, VHL mutation and 3p loss of heterozygosity were found in all regions of the tumor samples, while other common mutations recognized as driver mutations (SETD2, PBRM1, MTOR, SETD2, BAP1, KDM5C, TSC1.) were present heterogeneously
The phosphoinositide 3-kinase (PI3K)-AKT mammalian target of rapamycin is a serine/threonine kinase which exists in two different complexes: the mTOR Complex 1 and the mTORC2 [56]
Summary
Renal cell carcinoma (RCC) represents 5% of all cancers in men and 3% in women. In 2018, it was estimated that about 65,340 new diagnoses of RCC and 14,970 RCC-related deaths occurred in United States [1]. A new class of compounds, immune-checkpoint inhibitors, has been evaluated in several trials for advanced/metastatic malignancies These agents restore immune response against tumors through the inhibition of immune-checkpoint receptors or ligands such as: programmed death receptor 1/programmed death receptor ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyteassociated protein 4 (CTLA-4). A phase-III trial showed, for the first time, that the association between nivolumab and the CTLA-4 inhibitor ipilimumab improved the survival and other clinical outcomes of a specific population of patients with metastatic RCC [21]. The achievement of stable and durable responses still represents a goal which is achievable only in a minority of patients In this scenario, the evaluation of mechanisms related to resistance to treatment may be a critical issue. We focus our attention on possible mechanisms related to combination strategy resistance and possible approaches to overcoming these mechanisms
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
