New horizons in kidney cancer: A review of novel targeted and combination therapies from ۲۰۲۰-۲۰۲۴

Kidney cancer, specifically renal cell carcinoma (RCC), has seen significant advancements in its treatment over the last two decades. RCC accounts for approximately ۸۵% of all kidney cancers and represents a major cause of cancer-related deaths globally. Despite advancements in early detection and surgical techniques, many patients are diagnosed with advanced or metastatic disease, where prognosis remains poor. Advanced RCC has historically had a poor prognosis due to the lack of effective treatment options. However, the development of targeted therapies that inhibit angiogenesis and tumor growth pathways has revolutionized the management of advanced RCC. These therapies primarily focus on the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. Tyrosine kinase inhibitors (TKIs), VEGF inhibitors, and mTOR inhibitors became the cornerstone of RCC treatment throughout the ۲۰۰۰s and ۲۰۱۰s, dramatically altering the disease landscape. In recent years, combination approaches that integrate targeted therapies with immune checkpoint inhibitors (ICIs) have become increasingly central to the treatment paradigm. These combinations aim to enhance both anti-tumor immunity and inhibition of tumor angiogenesis, offering improved clinical outcomes compared to monotherapy approaches. The period from ۲۰۲۰ to ۲۰۲۴ has seen further advancements in this direction, with new drug approvals and combination regimens pushing the boundaries of efficacy, safety, and overall patient survival. Materials and Methods: This review examines data from clinical trials, real-world studies, and FDA drug approvals from ۲۰۲۰ to ۲۰۲۴ to evaluate the impact of novel targeted therapies and combination regimens in treating RCC. Specific focus is given to TKIs, VEGF inhibitors, mTOR inhibitors, and combinations of these agents with ICIs. We focused on important studies like CheckMate ۹ER, JAVELIN Renal ۱۰۱, and CLEAR, which tested new combinations of ICIs and TKIs. This review combines the latest findings to explain new treatments and their effectiveness in managing advanced RCC. Results: Combination therapies, particularly those involving TKIs and ICIs, have set new standards for first-line treatment, demonstrating significant improvements in progression-free survival (PFS) and overall survival (OS). While progress has been significant, challenges remain, including resistance to therapy, drug-related toxicities, and the high cost of treatment. Intrinsic and acquired resistance to targeted therapies is an ongoing issue, as tumors adapt to bypass angiogenic inhibition or develop alternative growth pathways. Despite these challenges, biomarker research is making strides, with efforts focused on identifying predictive indicators to optimize personalized treatment regimens. Conclusion: In conclusion the advancements in targeted therapies for RCC from ۲۰۲۰ to ۲۰۲۴, particularly in combination with immune checkpoint inhibitors, have led to substantial improvements in patient outcomes, including prolonged survival and higher response rates. Despite the enhanced efficacy, treatment-related toxicities remain a significant challenge, emphasizing the need for careful management of adverse effects. The future of RCC treatment lies in optimizing these combinations, developing biomarkers to personalize therapy, and overcoming resistance mechanisms to improve long-term outcomes. As research continues to refine these approaches, the outlook for patients with advanced RCC is increasingly positive, with improved survival rates and more personalized care pathways on the horizon.

کلیدواژه ها:

Renal cell carcinoma (RCC) ، Kidney cancer ، Targeted therapy ، Combination therapy ، Cancer immunotherapy