Targeted therapies in bladder cancer: signaling pathways, applications, and challenges.

Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.

Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.

Chiral drugs usually contain chiral centers, which are present as single enantiomers or racemates. Compared with achiral drugs, they have significant advantages in safety and efficacy with high stereoselectivity. Of these drugs, chirality not only exerts influence on the solubility and pharmacokinetic characteristics but also has specific mechanistic characteristics on their targets. We noted that small molecules with unique chiral properties have emerged as novel components of antitumor drugs approved by the FDA in decade. Since approved, these drugs have been continuously explored for new indications, new mechanisms, and novel combinations. In this mini review, recent research progress of twenty-two FDA-approved chiral small molecular-targeted antitumor drugs from 2011 to 2019 is summarized with highlighting the potential and advantages of their applications. We believe that these updated achievements may provide theoretical foundation and stimulate research interests for optimizing drug efficacy, expanding clinical application, overcoming drug resistance, and advancing safety in future clinical administrations of these chiral targeted drugs.