Check point inhibitors a new era in renal cell carcinoma treatment

Abstract

In the United States, the estimated number of new cases of renal cell carcinoma (RCC) is approximately 65,000 case with about 15,000 deaths in the year of 2018 (Siegel et al. in CA Cancer J Clin 68(1):7, 2018). RCC as an immunogenic malignancy is supported by many theories and facts which include tumor richness of lymphocytes infiltrate, the occurrence of spontaneous tumor regression, and the proved effect of traditional immunotherapy (Finke et al. in J Immunother 11(1):1-11, 1992), all these factors support the potential therapeutic effect of the novel immunotherapeutic agents in RCC. Historically, complete tumor regression in metastatic RCC is achievable in a minority of patients through traditional immunotherapies such as high-dose interleukin-2 (IL-2) (Fyfe et al. in J Clin Oncol 13(3):688, 1995) and interferon-alfa (IFNa) (Negrier et al. in N Engl J Med 338(18):1272, 1998); however due to the significant rate of toxicities and low efficacy; accordingly the targeted therapy with tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor-antibodies (VEGF) became the standard and prevalent treatment approach for advanced RCC both in front and subsequent lines of therapy (Escudier et al. in Ann Oncol. 25(Suppl 3):iii49-iii56, 2014). A new avenue of immunotherapy utilizing novel strategy to block immune checkpoints has emerged in a new era for RCC treatment (Ascierto et al. in J Transl Med 12:291, 2014). Results from clinical trials are encouraging in both front-line and second-line settings, in a phase III trial (CheckMate 025) nivolumab compared to everolimus improved overall survival in previously treated metastatic RCC who had progressed on prior treatment with targeting agents (Motzer et al. in N Engl J Med 373:1803, 2015). CheckMate 214, a phase III trial, demonstrated superior overall survival and objective response with combined checkpoint inhibitors compared to sunitinib in Treatment-Naïve Advanced RCC among intermediate- and poor-risk group (Motzer et al. in N Engl J Med. 378(14):1277-1290, 2018). In this review, we discuss the systemic Immunotherapy with checkpoint inhibitors that have been approved or are currently being investigated in RCC, clinical experience with these agents, and its future development.

<p>KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo</p>

“…1 In the United States, more than 65, 340 newly diagnosed RCC patients and approximately 14, 970 deaths in 2018. [2][3][4] While in 2019, there were 73, 820 new diagnosed RCC patients and approximately 14, 770 deaths. [2][3][4] Clear cell renal cell carcinoma (ccRCC) represents the highly aggressive renal malignant tumor which accounts for nearly 80% of renal cell carcinoma.…”

“…[2][3][4] While in 2019, there were 73, 820 new diagnosed RCC patients and approximately 14, 770 deaths. [2][3][4] Clear cell renal cell carcinoma (ccRCC) represents the highly aggressive renal malignant tumor which accounts for nearly 80% of renal cell carcinoma. 5 Existing traditional treatments, such as surgical resection, radiation and chemotherapy, seem to be ineffective against this highly aggressive tumor.…”

Outcomes of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy After Immuno-oncology Checkpoint Inhibitors

“…Recently, immuno-oncology (IO) therapeutic agents changed the treatment paradigm for mRCC by blocking immune checkpoints (eg, programmed death-1 [PD-1]/PDligand 1 [PD-L1]) and restoring tumor-specific T-cellmediated immune responses [10]. IO agents demonstrated antitumor activity and durable responses in pretreated and treatment-naïve mRCC [11][12][13].…”

Role of systemic inflammatory response markers in urological malignancy

“…Recently, in addition to cytotoxic agents, molecular-targeted drugs and immune checkpoint inhibitors have been introduced as new treatment options in patients with urological cancers, such as metastatic RCC and metastatic UC. [24][25][26] The role of molecular markers in appropriate patient selection has also been investigated. 27 Even in such circumstances, there have been an increasing number of clinical studies evaluating the role of SIR markers in cancer patients.…”