Radiation therapy, tissue radiosensitization, and potential synergism in the era of novel antibody-drug conjugates.

Antibody-drug conjugates (ADCs) represent a therapeutic class of agents designed to selectively deliver cytotoxic payloads to cancer cells. With the increasingly positioning of ADCs in the clinical practice, combinations with other treatment modalities, including radiation therapy (RT), will open new opportunities but also challenges. This review evaluates ADC-RT interactions, examining therapeutic synergies and potential caveats. ADC payloads can be radiosensitizing, enhancing cytotoxicity when used in combination with RT. Antigens targeted by ADCs can have various tissue expressions, resulting in possible off-target toxicities by tissue radiosensitization. Notably, the HER-2-directed ADC trastuzumab emtansine has appeared to increase the risk of radionecrosis when used concomitantly with brain RT, as glial cells can express HER2, too. Other possible organ-specific effects are discussed, such as pulmonary and cardiac toxicities. The lack of robust clinical data on the ADC-RT combination raises concerns regarding specific side effects and the ultimate trade-off of toxicity and safety of some combined approaches. Clinical studies are needed to assess ADC-RT combination safety and efficacy.

A comprehensive update of hormone-related pharmacokinetic variations associated with breast cancer drugs.

INTRODUCTION: Drugs available for the treatment of breast cancer are increasing, yielding improved oncological outcomes. The efficacy and safety of anticancer drugs significantly depend on pharmacokinetic profiles, which could be influenced by several factors, such as sex hormones. AREAS COVERED: This article discusses the potential hormone-related pharmacokinetic influences on novel breast cancer pharmacotherapies. EXPERT OPINION: Recently approved drugs for the treatment of breast cancer belong to different classes, each with unique pharmacokinetic profile. The impact of hormones, such as estrogen and progesterone, may occur at different steps of drug metabolism. Key effects of sex hormones ha ve been reported on multidrug-resistant transporters and enzymes involved in the liver metabolism of drugs, such as cytochromes. Nevertheless, no data is currently available to establish hormone-related metabolic interactions that may account for variability in drug scheduling and selection. Whereas we recognize influences may occur, we do not assume hormones alone can yield clinically significant metabolic changes. Rather, we believe that hormonal influences should be considered along with other elements that may affect drugs metabolism, such as concomitant medications, age-related pharmacokinetic changes, and genetic polymorphisms, in order to deliver treatment personalization and ensure better tolerability and safety of anticancer treatments.