Cancer invasion and metastasis are critical factors that influence patient prognosis. Carbonic anhydrase IX (CA IX) and carbonic anhydrase XII (CA XII) are key regulators of hypoxia and pH homeostasis in the tumor microenvironment (TME). It has been verified that both CA IX and CA XII play significant roles in promoting tumor metastasis in recent years, but most of the literature tends to treat them as separate entities rather than exploring their synergistic effects. This review provides a comprehensive overview of the roles of CA IX and CA XII in tumor invasion and metastasis, along with their clinical applications, including their spatial distribution characteristics, molecular mechanisms that facilitate tumor metastasis, and their potential for clinical translation. Moreover, this review incorporates the classical tumor core–invasive front model to propose a metabolic coupling model of CA IX and CA XII, offering a fresh perspective on precision therapies that target tumor metabolism. By emphasizing the metabolic coupling between these two molecules, this review offers new insights distinct from previous studies and highlights the clinical therapeutic potential of simultaneously targeting both during treatment. It sheds new light on future research and clinical applications, aiming to enhance the prognosis of cancer patients through innovative therapeutic strategies.

The hypoxic microenvironment within breast cancer tumors leads to the sustained activation of hypoxia-inducible factors (HIFs), notably HIF-1α, which, in turn, triggers adaptive responses such as angiogenesis and metabolic reprogramming. These processes contribute to tumor invasion, progression, metastasis, and therapy resistance. Although a substantial portion of the human genome is transcribed into non-coding RNAs (ncRNAs), which have been shown to play key regulatory roles in the development and progression of breast cancer, the interplay between HIFs and ncRNAs—and how such crosstalk influences breast cancer pathogenesis—remains poorly understood. This review aims to systematically outline the mechanisms of hypoxia-related signaling and ncRNA function in breast cancer, with a focus on their molecular interactions in disease progression and their potential clinical implications.

Background/Objectives: Spatholobi Caulis (SPC) is a medicinal plant that mainly grows in China and Southeast Asian countries and commonly used in clinics; the pharmacokinetic characteristics in humans need to be determined. This study was to establish the physiologically based pharmacokinetic (PBPK) models of multiple active constituents from SPC in rats, and predict the pharmacokinetic properties of rats with different dosages and extrapolated to humans. Methods: The parameters were collected based on our previous study and by prediction using ADMET Predictor software predict. The PBPK models for 3′-methoxydadizein (1), 8-O-methylretusin (2), daidzin (3), and isolariciresinol (4) administered orally to rats were established using GastroPlus software. These models were employed to simulate the pharmacokinetic properties in rats across various dosages, and subsequently extrapolated to humans. The calculated parameters including C_max, T_max, and AUC were compared with observed values. The accuracy of the PBPK models was assessed using fold-error (FE) values. Result: The FE values ranged from 1.03 to 1.52, meeting the PBPK model regulations where FE should be less than 2. The sensitivity analysis focusing on the absorption amount and AUC_0→t of these four constituents in humans was also conducted. These results confirm the successful establishment of PBPK models of these four constituents from SPC in this study, and these models were applicable to predict pharmacokinetics across various doses and extrapolate across species. Conclusions: The PBPK models of four constituents can be used to predict the pharmacokinetic characteristics in humans after oral administration of SPC and provide useful data for safe and rational medication in clinical practice.