University Hospital for Tumors, University Hospital Center Sestre milosrdnice
Abstract
Targeted therapy has been the standard of care for the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), antibodies to circulating VEGF receptor (bevacizumab) and m-TOR inhibitors (temsirolimus, everolimus). New immune-based therapies are emerging as a promising treatment for mRCC. Immune checkpoint blockade has shown clinically signifi cant antitumor response. Monoclonal antibodies against immune checkpoint blockade molecules including PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) have become a major focus in the immune-based therapy since it has been reported that they have impressive antitumor eff ects.
The most studied inhibitors in the PD-1 pathway are: nivolumab, pembrolizumab and atezolizumab. Based on the results of the phase III clinical trial (CheckMate025) nivolumab, humanized monoclonal IgG4 antibody against PD-1, is the only agent that is approved by the FDA for the second-line treatment of mRCC. Ipilimumab is the fi rst-in-class immunotherapeutic for blockade of CTLA-4. The immunotherapy combinations have demonstrated promising results in a randomized
trials. The use of cancer treatment vaccines is another approach to immunotherapy and will be systematically evaluated in the future.
Immunotherapy has demonstrated great clinical potential and it represents crucial component of mRCC treatment. Developing immunotherapy to the point of clinical utility presents a number of issue and challenges, and more rigorous studies are needed.Ciljana terapija danas predstavlja osnovicu sistemskog liječenja metastatskog raka bubrega (mRB), a standard liječenja su tirozin-kinazni inhibitori (sunitinib, sorafenib, pazopanib, aksitinib), protutijela na cirkulirajući VEGF receptor (bevacizumab) i m-TOR inhibitori (temsirolimus, everolimus). Noviji imunoterapijski principi predstavljaju značajne iskorake u liječenju mRB. Jedna forma imunoterapije je inhibicija imunoloških kontrolnih točaka (eng. immune checkpoint). Blokiranjemjednog od dva najistraživanija imunološka receptora; antigen 4 povezan s aktivnošću citotoksičnih T-limfocita (CTLA-4) i receptor programirane stanične smrti (PD-1), potenciramo antitumorski imunološki odgovor.
Među najistraživanije anti-PD-1 inhibitore ubrajamo: nivolumab, pembrolizumab i avelumab. Nivolumab je ljudsko monoklonalno antitijelo kojega je Američka agencija za hranu i lijekove odobrila u drugoj liniji liječenje mRB, a na osnovi rezultata kliničke studije faze III (CheckMate025). Ipilimumab je prvi registrirani checkpoint inhibitor koji blokira inhibitorni signal (CTLA-4 receptor) na površini citotoksičnih T limfocita. Veliki pomak u imunoterapiji mRB postigut je primjenom
konkomitantnih protokola liječenja. Novija istraživanja primjene imunoterapije u liječenju raka bubrega uključuju i pronalaženje cjepiva koje bi prepoznavalo i uništavalo promijenjene tumorske stanice.
Imunoterapija ima jasno mjesto i veliki potencijal u liječenju raka bubrega. Ipak, postoji još niz problema i pitanja te su potrebna brojna daljnja istraživanja kako bi se iskoristio njen puni potencijal
