Immunotherapy-Associated Renal Dysfunction in Metastatic Cancer: An Emerging Challenge in Onco-Nephrology.

Background: Immune checkpoint inhibitors (ICIs) have significantly modified the management of metastatic cancers; however, their nephrotoxic potential remains underappreciated. While acute kidney injury (AKI) is a known immune-related adverse event, the subacute spectrum of kidney injury-termed acute kidney disease (AKD)-has not been adequately explored in this setting.

Methods: We conducted a retrospective cohort study in 226 adult patients with metastatic solid tumors who received ICIs between 2017 and 2023 at a single tertiary care center.

Circulating tumor DNA: a biomarker for oncology drug development in phase I clinical trials?

Introduction: Circulating tumor DNA (ctDNA) is a noninvasive and promising biomarker for cancer diagnosis, prognosis, and therapeutic monitoring, offering significant potential for real-time insights into tumor dynamics when compared to traditional tissue-based biopsies. Phase I oncology clinical trials, which primarily focus on assessing the safety, pharmacodynamics, and early activity of novel cancer therapies, might find in the unique biological characteristics of ctDNA, a valuable biomarker to boost the efficiency of testing novel agents.

Areas Covered: This review explores the utility of ctDNA as a biomarker in phase I trials, discussing its biological and technical features, clinical relevance, current limitations, and future potential in advancing early clinical drug development.

From Dose-Finding to Dose-Optimization in Early-Phase oncology clinical trials.

Dose optimization in Phase I oncology trials balances therapeutic efficacy and patient safety. Traditional dose-escalation methods, such as the 3 + 3 design, primarily focus on safety, often resulting in prolonged exposure to subtherapeutic or excessively toxic doses. Additionally, these methods may fail to account for modern therapies' complex pharmacokinetics and pharmacodynamics, including targeted agents and immunotherapies.

An update on promising and emerging protein kinase B/AKT inhibitors for breast cancer.

Introduction: The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role in treatment resistance. This pathway's involvement in breast carcinogenesis and its link to treatment resistance underscores the significance of targeting it in BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due to toxicity issues that hinder their development.

Innovative payloads for ADCs in cancer treatment: moving beyond the selective delivery of chemotherapy.

Antibody-drug conjugates (ADCs) have emerged as a transformative approach in cancer therapy by enhancing tumor targeting and minimizing systemic toxicity compared to traditional chemotherapy. Initially developed with chemotherapy agents as payloads, ADCs have now incorporated alternative payloads, such as immune-stimulating agents, natural toxins, and radionuclides, to improve therapeutic efficacy and specificity. A significant advancement in ADC technology is the integration of Proteolysis Targeting Chimeras (PROTACs), which enable the precise degradation of cellular targets involved in tumorigenesis.