maytansine and Renal-Insufficiency--Chronic

EGFR and HER2 are found overexpressed and/or activated in many different human malignancies (e.g. breast and colon cancer), and a number of drugs specifically targeting these two tyrosine kinases have been developed over the years as anticancer agents. In the present review, the renal safety profile of presently available agents targeting either HER2 or EGFR will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, even though renal toxicity is not so common with these agents, it may nevertheless happen, especially when these agents are combined with traditional chemotherapeutic agents. As a whole, kidney impairment or dialysis should not be regarded per se as reasons not to administer or to stop an active anti-HER or anti-EGFR anticancer treatment, especially given the possibility of significantly improving the life expectancy of many cancer patients with the use of these agents.

Topics: Acute Kidney Injury; Ado-Trastuzumab Emtansine; Afatinib; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; Lapatinib; Maytansine; Neoplasms; Protein Kinase Inhibitors; Quinazolines; Receptor, ErbB-2; Renal Dialysis; Renal Insufficiency, Chronic; Trastuzumab

Myofibroblasts, or activated fibroblasts, play a critical role in the process of renal fibrosis. Targeting myofibroblasts to inhibit their activation or induce specific cell death has been considered to be an effective strategy to attenuate renal fibrosis. However, specific biomarkers for myofibroblasts are needed to ensure the efficacy of these strategies. Here, we verified that CD248 was mainly expressed in myofibroblasts in patients with chronic kidney disease, which was inversely correlated with renal function. The same result was also confirmed in renal fibrotic mice induced by unilateral ureteral obstruction and aristolochic acid nephropathy. By using an antibody-drug conjugate (ADC) named IgG78-DM1, in which maytansinoid (DM1) was linked to a fully human antibody IgG78 through an uncleavable SMCC linker, we demonstrated that it could effectively bind with and kill CD248

Topics: Animals; Antigens, CD; Antigens, Neoplasm; Drug Delivery Systems; Fibrosis; Immunoconjugates; Male; Maytansine; Mice; Myofibroblasts; Renal Insufficiency, Chronic