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Renal cell carcinoma is a malignant tumor that arises in the kidney parenchyma. For many years, sunitinib has represented the mainstay of medical treatment for metastatic renal cell carcinoma. Herein, we present the case of a 66-year-old woman with metastatic clear cell renal carcinoma undergoing treatment with sunitinib for two years that developed encephalic leukocytoclastic vasculitis, probably due to a paraneoplastic syndrome.

Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) represent an effective therapeutic strategy for cancer patients harboring germline and somatic aberrations in DNA damage repair (DDR) genes. BRCA1/2 mutations occur at 1–7% across biliary tract cancers (BTCs), but a broader spectrum of DDR gene alterations is reported in 28.9–63.5% of newly diagnosed BTC patients. The open question is whether alterations in genes that are well established to have a role in DDR could be considered as emerging predictive biomarkers of response to platinum compounds and PARPi. Currently, data regarding PARPi in BTC patients harboring BRCA and DDR mutations are sparse and anecdotal; nevertheless, a variety of clinical trials are testing PARPi as monotherapy or in combination with other anticancer agents. In this review, we provide a comprehensive overview regarding the genetic landscape of DDR pathway deficiency, state of the art and future therapeutic implications of PARPi in BTC, looking at combination strategies with immune-checkpoint inhibitors and other anticancer agents in order to improve survival and quality of life in BTC patients.

Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.

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