Molecular‐targeted therapy in advanced renal cell carcinoma based on pharmacokinetics, pharmacodynamics and pharmacogenetics: A proposed strategy

Abstract

In advanced renal cell carcinoma, a transition of drug therapies from cytokines to molecular‐targeted drugs and immune‐oncology drugs provides more clinical benefits to patients, while adequate management is required for various and sometimes serious adverse events. At present, the relationship between the pharmacokinetics of many drugs and their effectiveness or adverse events has been elucidated, and therapeutic drug monitoring is being applied to some immunosuppressive, anti‐epileptic and antibacterial drugs in daily clinical practice. Most of the molecular‐targeted drugs used in patients with renal cell carcinoma are orally active, and are affected by absorption and disposition, which can be different for each individual. The monitoring of the circulating drug concentration could be beneficial to patients by providing information for the adjustment of drug dose and the maintenance of a therapeutic plasma concentration range. Genetic polymorphisms are known to be involved in pharmacokinetics, and cause individual differences in clinical efficacy and adverse events. Therefore, a more scientific strategy should be used in regard to the treatment of patients with advanced renal cell carcinoma treated with molecular‐targeted drugs by accumulating evidence on pharmacodynamics and pharmacogenetics.

C‐reactive protein/albumin ratio is a predictive factor for prognosis in patients with metastatic renal cell carcinoma

“…In recent decades, molecular-targeted therapies have been generally used for treatment of mRCC. [1][2][3][4][5][6][7][8][9][10][11] As prognoses in mRCC have improved, more precise stratifications based on risk factors have been required. In the molecular-targeted therapy era, the IMDC risk classification is a standard riskbased stratification.…”

“…In recent decades, molecular‐targeted therapies have been generally used for treatment of mRCC . As prognoses in mRCC have improved, more precise stratifications based on risk factors have been required.…”

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/β-catenin signaling pathways in clear cell renal cell carcinoma

“…Moreover, these patients exhibit insensitivity to conventional radiotherapy and chemotherapy following surgical procedures [ 3 ]. Consequently, there exists a pressing demand for biomarkers that can effectively diagnose pathological characteristics and subsequently enhance the prognostic outcomes of ccRCC patients, particularly in the targeted therapy era [ 4 ].…”

KIF20B promotes the progression of clear cell renal cell carcinoma by stimulating cell proliferation

“…In 2017, there were more than 60 thousand newly diagnosed RCC patients with nearly 15,000 deaths in the United States (Hsieh et al, 2017;Smaldone et al, 2017). Among multiple treatments, generally, targeted therapy is the most effective method to combat this disease (Chen et al, 2018;Tsuchiya, 2018). Some genes, such as PTEN and CA9, have been confirmed to participate in RCC pathogenesis and served as therapeutic targets for the treatment of RCC (Kim et al, 2017;Voss et al, 2018).…”