Drug development, from preclinical to clinical studies, is a lengthy and complex process. There is an increased interest in the Kingdom of Saudi Arabia (KSA) to promote innovation, research and local content including clinical trials (Phase I-IV). Currently, there are over 650 registered clinical trials in Saudi Arabia, and this number is expected to increase. An important part of drug development and clinical trials is to assure the safe and effective use of drugs. Clinical pharmacology plays a vital role in informed decision making during the drug development stage as it focuses on the effects of drugs in humans. Disciplines such as pharmacokinetics, pharmacodynamics and pharmacogenomics are components of clinical pharmacology. It is a growing discipline with a range of applications in all phases of drug development, including selecting optimal doses for Phase I, II and III studies, evaluating bioequivalence and biosimilar studies and designing clinical studies. Incorporating clinical pharmacology in research as well as in the requirements of regulatory agencies will improve the drug development process and accelerate the pipeline. Clinical pharmacology is also applied in direct patient care with the goal of personalizing treatment. Tools such as therapeutic drug monitoring, pharmacogenomics and model informed precision dosing are used to optimize dosing for patients at an individual level. In KSA, the science of clinical pharmacology is underutilized and we believe it is important to raise awareness and educate the scientific community and healthcare professionals in terms of its applications and potential. In this review paper, we provide an overview on the use and applications of clinical pharmacology in both drug development and clinical care.

Ca²⁺ homeostasis is dysregulated in cancer cells and affects processes such as tumorigenesis, angiogenesis, autophagy, progression, and metastasis. Emerging evidence has suggested that endolysosomal cation channels sustain several cancer hallmarks involving proliferation, metastasis, and angiogenesis. Here, we investigate the role of TPC1-2, TRPML1-3, and P2×4 in cancer, with a particular focus on the role of TPC2 in cancer development, melanoma, and other cancer types as well as its endogenous and exogenous modulators. It has become evident that TPC2 plays a role in cancer; however, the precise mechanisms underlying its exact role remain elusive. TPC2 is a potential candidate for cancer biomarkers and a druggable target for future cancer therapy.

Metastatic cancer is one of the major causes of cancer-related mortalities. Metastasis is a complex, multi-process phenomenon, and a hallmark of cancer. Calcium (Ca²⁺) is a ubiquitous secondary messenger, and it has become evident that Ca²⁺ signalling plays a vital role in cancer. Ca²⁺ homeostasis is dysregulated in physiological processes related to tumour metastasis and progression—including cellular adhesion, epithelial–mesenchymal transition, cell migration, motility, and invasion. In this review, we looked at the role of intracellular and extracellular Ca²⁺ signalling pathways in processes that contribute to metastasis at the local level and also their effects on cancer metastasis globally, as well as at underlying molecular mechanisms and clinical applications. Spatiotemporal Ca²⁺ homeostasis, in terms of oscillations or waves, is crucial for hindering tumour progression and metastasis. They are a limited number of clinical trials investigating treating patients with advanced stages of various cancer types. Ca²⁺ signalling may serve as a novel hallmark of cancer due to the versatility of Ca²⁺ signals in cells, which suggests that the modulation of specific upstream/downstream targets may be a therapeutic approach to treat cancer, particularly in patients with metastatic cancers.

The role of endolysosomal Ca²⁺ signalling in immunity has been a subject of increasing interest in recent years. Here, we discuss evolving knowledge relating to the contribution of endolysosomal Ca²⁺ channels that include TPCs, TRPMLs, and P2X4R in physiological processes related to innate and adaptive immunity—including phagocytosis, inflammation, cytokine/chemokine release, dendritic, natural killer, and T cell activation and migration—and we underscore the paucity of clinical studies in this field. Emerging biomedical and translational data have led to important new insights into the critical roles of these channels in immune cell function and the regulation of innate and adaptive immune responses. The evolving immunological significance of endolysosomal Ca²⁺ signalling warrants further investigations to better characterize the roles of these channels in immunity in order to expand our knowledge about the pathology of inflammatory and autoimmune diseases and develop endolysosomal Ca²⁺ channels as viable biomarkers and therapeutic and preventive targets for remodelling the immune response.