In the realm of cancer therapeutics, targeting the hypoxia-inducible factor (HIF) pathway has emerged as a promising strategy. This study delves into the intricate web of HIF-associated mechanisms, exploring avenues for future anticancer therapies. Framing the investigation within the broader context of cancer progression and hypoxia response, this article aims to decipher the pivotal role played by HIF in regulating genes influencing angiogenesis, cell proliferation, and glucose metabolism. Employing diverse approaches such as HIF inhibitors, anti-angiogenic therapies, and hypoxia-activated prodrugs, the research methodologically intervenes at different nodes of the HIF pathway. Findings showcase the efficacy of agents like EZN-2968, Minnelide, and Acriflavine in modulating HIF-1α protein synthesis and destabilizing HIF-1, providing preliminary proof of HIF-1α mRNA modulation and antitumor activity. However, challenges, including toxicity, necessitate continued exploration and development, as exemplified by ongoing clinical trials. This article concludes by emphasizing the potential of targeted HIF therapies in disrupting cancer-related signaling pathways.

Bispecific antibodies (BsAbs) have shown potential in cancer treatment and have become a rapidly growing field in cancer immunotherapy. Unlike monoclonal antibodies with two identical binding sites, BsAbs simultaneously bind two distinct epitopes on the same or different antigens, allowing for a range of mechanisms of action, including engaging immune cells to kill cancer cells and blocking signaling pathways. Despite regulatory approvals for hematological malignancies in the last decade, their clinical success in solid malignancies has been lacking until recently. There are currently five BsAbs approved by the FDA in the United States for solid tumors—amivantamab, tarlatamab, tebentafusp, zanidatamab and zenocutuzumab—and two BsAbs approved in China—cadonilimab and ivonescimab. Currently, several BsAbs are under clinical development for solid tumors, but are mostly in early phase I and II trials. This review provides an overview of the basic mechanism of action of BsAbs, current FDA-approved BsAbs, and current BsAbs under clinical development, their challenges in clinical use, the management of toxicities, and future directions.

Unexpected Rasburicase-Induced Hemolysis in a Patient With Normal Glucose-6-Phosphate Dehydrogenase Activity

The treatment landscape of oncogene-driven non-small-cell lung cancer (NSCLC) has evolved substantially with the development of targeted therapies directed against actionable molecular alterations. Tyrosine kinase inhibitors (TKIs) remain the cornerstone of treatment for many driver-defined subsets; however, acquired resistance, central nervous system progression, and tumor heterogeneity continue to limit long-term disease control. This review examines the mechanistic foundations, clinical evidence, resistance patterns, and emerging therapeutic roles of TKIs, antibody–drug conjugates (ADCs), and bispecific antibodies (bsAbs) in oncogene-driven NSCLC. Relevant preclinical studies, clinical trials, and recent therapeutic advances across major actionable driver alterations were reviewed and compared. TKIs provide potent and selective inhibition of oncogenic signaling and remain the preferred frontline therapy in most molecular subgroups, whereas ADCs offer targeted payload delivery that may overcome diverse resistance mechanisms, and bsAbs provide dual-target blockade and immune-mediated antitumor activity. Emerging evidence supports the expanding role of ADCs and bsAbs in post-TKI settings and selected biomarker-defined populations. Resistance mechanisms differ across therapeutic classes and include secondary target alterations, bypass pathway activation, antigen loss, payload resistance, and receptor adaptation. Collectively, these modalities are increasingly being integrated into biomarker-guided treatment strategies, with future management likely to rely on rational sequencing and combination approaches tailored to resistance mechanisms, target expression, central nervous system involvement, and tumor heterogeneity.

From the 2026 National Summit on Hematologic Cancers