Leveraging multi-omics data to empower quantitative systems pharmacology in immuno-oncology.

Understanding the intricate interactions of cancer cells with the tumor microenvironment (TME) is a pre-requisite for the optimization of immunotherapy. Mechanistic models such as quantitative systems pharmacology (QSP) provide insights into the TME dynamics and predict the efficacy of immunotherapy in virtual patient populations/digital twins but require vast amounts of multimodal data for parameterization. Large-scale datasets characterizing the TME are available due to recent advances in bioinformatics for multi-omics data. Here, we discuss the perspectives of leveraging omics-derived bioinformatics estimates to inform QSP models and circumvent the challenges of model calibration and validation in immuno-oncology.

Un mecanismo nefrogénico subyace a la poliuria inducida por dexmedetomidina: informe de un caso / Nephrogenic mechanism underlies dexmedetomidine-induced polyuria: A case report

La dexmedetomidina, agonista del adrenorreceptor α, se utiliza cada vez más como agente sedativo-hipnótico y analgésico, aunque su popularidad suscita preocupación acerca de los efectos secundarios de dicho fármaco.La bradicardia y la hipotensión son efectos adversos comunes, pero también existen diversos informes de gasto urinario excesivo, posiblemente debido a la secreción de vasopresina y a la permeabilidad de los conductos colectores.La poliuria se resuelve normalmente con la discontinuación del fármaco, no habiéndose reportado morbilidad significativa. La identificación temprana, la eliminación del agente y el tratamiento son imperativos para minimizar las complicaciones, principalmente natremia y síntomas neurológicos.Este informe de caso describe la poliuria relacionada con dexmedetomidina durante la anestesia general libre de opioides para cirugía mayor de cabeza y cuello. Nuestra hipótesis de etiología nefrogénica se ve reforzada por los datos analíticos obtenidos. También describimos cómo abordar la poliuria intraoperatoria. (AU)

Dexmedetomidine's α-adrenoreceptor agonism has been gaining popularity in the anesthetic room as a sedative-hypnotic and analgesic agent, and with extensive perioperative use rising concern about side effects is necessary.Bradycardia and hypotension are common but excessive urine output is increasingly reported, suggested mechanisms being vasopressin secretion and increasing permeability of the collecting ducts.Polyuria usually resolves with discontinuation of the drug and significant morbidity has not been reported. Early identification, removal of agent and treatment are imperative to minimize complications, mainly associated with natremia levels and neurological symptoms.This case report describes a dexmedetomidine-related polyuric syndrome during opioid-free general anesthesia for major head and neck surgery. A nephrogenic mechanism for the clinical effect is proposed and reinforced by analytical data obtained. An intra-operative polyuria approach is also delineated. (AU)

Beyond lectures and practical courses: Teaching pharmacology using imaginative pedagogical tools.

Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.

Finding new analgesics: Computational pharmacology faces drug discovery challenges.

Despite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation. Computational pharmacology is currently employed to face these challenges. In this review, we discuss the theory, methods, and applications of computational pharmacology in pain research. Computational pharmacology encompasses a wide variety of theoretical concepts and practical methodological approaches, with the overall aim of gaining biological insight through data acquisition and analysis. Data are acquired from patients or animal models with pain or analgesic treatment, at different levels of biological organization (molecular, cellular, physiological, and behavioral). Distinct methodological algorithms can then be used to analyze and integrate data. This helps to facilitate the identification of biological molecules and processes associated with pain phenotype, build quantitative models of pain signaling, and extract translatable features between humans and animals. However, computational pharmacology has several limitations, and its predictions can provide false positive and negative findings. Therefore, computational predictions are required to be validated experimentally before drawing solid conclusions. In this review, we discuss several case study examples of combining and integrating computational tools with experimental pain research tools to meet drug discovery challenges.

An account on the history of pharmacology in Spain.

Here we present an account on the history of pharmacology in Spain. Pharmacology as an independent science in Europe began with the creation of university chairs. Of particular relevance was the appointment in 1872 of Osswald Shmiedeberg as chairman of an Institute of Pharmacology at the University of Strassbourg, Germany. Teófilo Hernando pioneered in Spain the new emerging pharmacology at the beginning of the XX Century. He made a posdoctoral stay in the laboratory of Schmiedeberg, working on digitalis. In 1912 he won the chair of "Materia Médica y Arte de Recetar" at "Universidad Central of Madrid" (today, "Universidad Complutense de Madrid", UCM). He soon decided to transform such subject to the emerging modern pharmacology, with the teaching of experimental pharmacology in the third course of medical studies and clinical therapeutics (today clinical pharmacology) in the sixth course. This was the status of pharmacology in 1920, supporting the view that Hernando was a pioneer of clinical pharmacology. However, the Spanish Civil War and the II Word War interropted this division of preclinical and clinical pharmacology; only in the 1980's was clinical pharmacolgy partially developed in Spain. From a scientific point of view, Hernando directly trained various young pharmacologists that extended the new science to various Spanish universities. Some of his direct disciples were Benigno Lorenzo Velázquez, Francisco García Valdecasas, Rafael Méndez, Tomás Alday, Gabriel Sánchez de la Cuesta, Dámaso Gutiérrez or Ramón P é rez-Cirera. One of the central research subject was the analysis of the effects of digitalis on the cat and frog heart. In the initiation of the 1970 s pharmacologists trained by those Hernando's students grew throughout various universities and the "Consejo Superior de Investigaciones Científicas" (CSIC). And hence, in 1972 the "Sociedad Española de Farmacología" (SEF) emerged. Later on, in the 1990's the "Sociedad Española de Farmacología Clínica (SEFC) also emerged. The relationship between the two societies is still weak. Out of the vast scope of the pharmacological sciences, Spanish pharmacologists have made relevant contributions in two areas namely, neuropsychopharmacology and cardiovacular pharmacology. Nonetheless, in other areas such as smooth muscle, gastroenterology, pharmacogenetics and hepatic toxicity, Spanish pharmacologists have also made relevant contributions. A succint description of such contributions is made. Finally, some hints on perspectives for the further development of preclinical and clinical pharmacology in Spain, are offered.

Physiological Indirect Response Model to Omics-Powered Quantitative Systems Pharmacology Model.

Over the past several decades, mathematical modeling has been applied to increasingly wider scopes of questions in drug development. Accordingly, the range of modeling tools has also been evolving, as showcased by contributions of Jusko and colleagues: from basic pharmacokinetics/pharmacodynamics (PK/PD) modeling to today's platform-based approach of quantitative systems pharmacology (QSP) modeling. Aimed at understanding the mechanism of action of investigational drugs, QSP models characterize systemic effects by incorporating information about cellular signaling networks, which is often represented by omics data. In this perspective, we share a few examples illustrating approaches for the integration of omics into mechanistic QSP modeling. We briefly overview how the evolution of PK/PD modeling into QSP has been accompanied by an increase in available data and the complexity of mathematical methods that integrate it. We discuss current gaps and challenges of integrating omics data into QSP models and propose several potential areas where integrated QSP and omics modeling may benefit drug development.

Defining and unpacking the core concepts of pharmacology: A global initiative.

BACKGROUND AND PURPOSE: Development of core concepts in disciplines such as biochemistry, microbiology and physiology have transformed teaching. They provide the foundation for the development of teaching resources for global educators, as well as valid and reliable approaches to assessment. An international research consensus recently identified 25 core concepts of pharmacology. The current study aimed to define and unpack these concepts. EXPERIMENTAL APPROACH: A two-phase, iterative approach, involving 60 international pharmacology education experts, was used. The first phase involved drafting definitions for core concepts and identifying key sub-concepts via a series of online meetings and asynchronous work. These were refined in the second phase, through a 2-day hybrid workshop followed by a further series of online meetings and asynchronous work. KEY RESULTS: The project produced consensus definitions for a final list of 24 core concepts and 103 sub-concepts of pharmacology. The iterative, discursive methodology resulted in modification of concepts from the original study, including change of 'drug-receptor interaction' to 'drug-target interaction' and the change of the core concept 'agonists and antagonists' to sub-concepts of drug-target interaction. CONCLUSIONS AND IMPLICATIONS: Definitions and sub-concepts of 24 core concepts provide an evidence-based foundation for pharmacology curricula development and evaluation. The next steps for this project include the development of a concept inventory to assess acquisition of concepts, as well as the development of case studies and educational resources to support teaching by the global pharmacology community, and student learning of the most critical and fundamental concepts of the discipline.

Modalidades Fisioterapêuticas no Manejo da Dor Neuropática Induzida pelo Tratamento do Câncer de Mama: Revisãoda Literatura / Physiotherapeutic Modalities in the Management of Neuropathic Pain Induced by Breast Cancer Treatment: Literature Review / Modalidades Fisioterapéuticas en el Manejo Del Dolor Neuropático Inducido por el Tratamiento del Cáncer de Mama: Revisión de la Literatura

A sobrevida de mulheres após o tratamento do câncer de mama tem aumentado em virtude de avanços na detecção precoce e terapias disponíveis. Porém, as sobreviventes comumente enfrentam efeitos adversos após o tratamento que representam grande carga física e psicológica. Além da fadiga, a dor é o sintoma persistente mais frequente após o tratamento. Objetivo: Sistematizar os resultados de ensaios clínicos randomizados sobre a intervenção fisioterapêutica na dor neuropática periférica induzida pelos tratamentos para o câncer de mama. Método: Busca realizada nas bases de dados MEDLINE via portal PubMed e Cochrane. Foram selecionados ensaios clínicos randomizados publicados a partir de 2017, em língua inglesa, que abordassem as modalidades fisioterapêuticas como intervenção, a dor neuropática periférica induzida por tratamentos oncológicos como desfecho, e mulheres sobreviventes ao câncer de mama como população de interesse. A qualidade metodológica dos estudos foi avaliada pela ferramenta Cochrane para o risco de viés. Resultados: Quatro estudos foram revisados na íntegra. Majoritariamente, os efeitos adversos do tratamento oncológico se devem a regimes quimioterápicos à base de taxanos. Os desfechos avaliados incluem, além da dor, demais sinais neuropáticos e influência nas atividades de vida diária. Os estudos variaram quanto à intervenção e fase de tratamento. Apenas um dos estudos demonstrou resultado significativamente positivo a favor do grupo intervenção. Conclusão: Estudos clínicos randomizados disponibilizam evidências escassas quanto aos efeitos positivos da intervenção fisioterapêutica na dor neuropática periférica induzida pelos tratamentos para o câncer de mama.

Women's survival after breast cancer treatment has increased due to advances in early detection and available therapies. However, great physical and psychological burden are the result of adverse effects that survivors commonly face. In addition to fatigue, pain is the most common persistent symptom after cancer treatment. Objective: Systematize the results of randomized clinical trials on physiotherapeutic intervention in peripheral neuropathic pain induced by breast cancer treatments . Method:The search was carried out on the MEDLINE databases via PubMed and Cochrane portals. Randomized clinical trials published since 2017 in English, that addressed physiotherapeutic modalities as intervention, peripheral neuropathic pain induced by oncological treatments as outcome were selected, and the population of interest were women surviving breast cancer. The Cochrane-risk-of-bias tool was applied to evaluate the methodological quality of the studies. Results: Four studies were fully reviewed. Most of the adverse effects of cancer treatment are due to taxane-based chemotherapy regimens. The outcomes assessed include, in addition to pain, other neuropathic signs and influence on activities of daily living. The studies varied in terms of intervention and treatment phase. Only one of the studies demonstrated a significantly positive result in favor of the intervention group. Conclusion: Randomized clinical studies provide scant evidence regarding the positive effects of physiotherapeutic intervention on peripheral neuropathic pain induced by breast cancer treatments.

La supervivencia de las mujeres después del tratamiento del cáncer de mama ha aumentado debido a los avances en la detección temprana y las terapias disponibles. Sin embargo, los supervivientes suelen enfrentarse a efectos adversos después del tratamiento que representan una gran carga física y psicológica. Además de la fatiga, el dolor es el síntoma persistente más común después del tratamiento del cáncer. Objetivo: Sistematizar los resultados de ensayos clínicos aleatorizados sobre intervención fisioterapéutica en el dolor neuropático periférico inducido por tratamientos para el cáncer de mama. Método: La búsqueda se realizó en las bases de datos MEDLINE a través de los portales PubMed y Cochrane. Se seleccionaron ensayos clínicos aleatorizados publicados desde 2017, en inglés, que abordaron modalidades fisioterapéuticas como intervención, dolor neuropático periférico inducido por tratamientos oncológicos como resultado y mujeres sobrevivientes de cáncer de mama como población de interés. La calidad metodológica de los estudios se evaluó mediante la herramienta Cochrane de Riesgo de Sesgo. Resultados: Se revisaron en su totalidad cuatro estudios. La mayoría de los efectos adversos del tratamiento del cáncer se deben a los regímenes de quimioterapia basados en taxanos. Los resultados evaluados incluyen, además del dolor, otros signos neuropáticos y su influencia en las actividades de la vida diaria. Los estudios variaron en términos de intervención y fase de tratamiento. Sólo uno de los estudios demostró un resultado significativamente positivo a favor del grupo de intervención. Conclusión: Los estudios clínicos aleatorizados aportan escasa evidencia sobre los efectos positivos de la intervención fisioterapéutica sobre el dolor neuropático periférico inducido por los tratamientos del cáncer de mama

The Concise Guide to PHARMACOLOGY 2023/24: Nuclear hormone receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16179. Nuclear hormone receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

The Concise Guide to PHARMACOLOGY 2023/24: Transporters.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

The Concise Guide to PHARMACOLOGY 2023/24: Catalytic receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16180. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Medicamentos: breve historia y su evolución el mercado global / Drugs: brief history and evolution the global market

La Historia del Medicamento tiene su origen ya en la vida y civilizaciones primitivas hasta la actualidad fantástica hoy en la Biotecnología Farmacéutica, en el escenario de las vacunas contra el Covid-19 que han salvado millones de vidas. Las plantas medicinales aún hoy son de uso común en la mayoría de los países de Latinoamérica. “Las Farmacopeas son un conjunto de normas sobre principios activos, productos farmacéuticos auxiliares, productos medicamentos o terminados, y métodos recomendados a fin de constatar si éstos las cumplen y que han sido publicados y reconocidos por la autoridad sanitaria competente.” Estas normas regulan el circuito de los medicamentos en los distintos países. El acceso a los medicamentos es un factor esencial para el uso adecuado de los mismos. Según la Organización Mundial de la Salud, la tercera parte de la población mundial no tiene acceso a medicamentos esenciales para la salud (más de 2,5 mil millones de seres humanos). Las compañías farmacéuticas de investigación dedicaron un total de 198.000 millones de USD en I+D en el año 2020 (último año con datos oficiales).Esto significa una inversión muy superior a otros sectores de Alta Tecnología. Así es 8,1 veces mayor que lo dedicado a la Industria Aeroespacial y de Defensa, 7,2 veces superior a la Industria Química y 1,2 veces que las de las compañías de Software y Servicios Informáticos.Para el año 2026 se estima se alcance un monto de 254 mil millones de USD.La Federación Europea de la Industria Farmacéutica (EFPIA) estima en 8.000 el número de medicamentos en ensayos clínicos (10% para enfermedades raras).(AU)

The main protagonist of Pharmacy is Medicine; Without it, there would be no such thing, and its companion, medicine, would be in a very bad light, for it would have lost its main purpose.”The History of Medicines has its origins in primitive life and civilizations until the present fantastic today in Pharmaceutical Biotechnology, in the scenario of vaccines against Covid-19 that have saved millions of lives. Medicinal plants are still in common use today in most Latin American countries. “The Pharmacopoeias are a set of standards on active ingredients, ancillary pharmaceutical products, medicinal or finished products, and recommended methods in order to verify whether they comply with them and that have been published and recognized by the competent health authority.” These rules govern the circuit of me- dicines in the various countries. Access to medicines is an essential factor for the proper use of medicines. According to the World Health Orga- nization, one third of the world’s population does not have access to essential health medicines (more than 2.5 billion human beings). Pharmaceutical research companies dedicated a total of USD 198,000 million in R+D in 2020 (the last year with official data). This means a much higher investment than other high-tech sectors. This is 8.1 times higher than that dedicated to the Aerospace and Defense Industry, 7.2 times higher than the Chemical Industry and 1.2 times that of Soft- ware and Computer Services companies.By 2026, it is estimated that it will reach an amount of USD 254 billion.The European Federation of the Pharmaceutical Industry (EFPIA) estimates the number of medicines in clinical trials at 8,000 (10% for rare diseases).(AU)

Development of bispecific T cell engagers: harnessing quantitative systems pharmacology.

Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development.