Trends in Pharmacological Sciences
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New articles

Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

September 23, 2022


Functional precision cancer medicine: drug sensitivity screening enabled by cell culture models

  • Åsmund Flobak,
  • Sigrid S. Skånland,
  • Eivind Hovig,
  • Kjetil Taskén,
  • Hege G. Russnes
First published:September 23, 2022
Functional precision medicine is a new, emerging area that can guide cancer treatment by capturing information from direct perturbations of tumor-derived, living cells, such as by drug sensitivity screening. Precision cancer medicine as currently implemented in clinical practice has been driven by genomics, and current molecular tumor boards rely extensively on genomic characterization to advise on therapeutic interventions. However, genomic biomarkers can only guide treatment decisions for a fraction of the patients.

September 10, 2022

Science & Society

Malnutrition vaccines for an imminent global food catastrophe

  • Peter J. Hotez
First published:September 10, 2022
Together with climate change, both the geopolitical events in Ukraine and social disruptions in supply chains from the COVID-19 pandemic could produce global food shortages or even mass starvation events. Promising new interventions include vaccines to prevent infectious causes of malnutrition or infections disproportionately causing death among the malnourished.

September 8, 2022


Nanodelivery of cGAS-STING activators for tumor immunotherapy

  • Jianfeng Guo,
  • Leaf Huang
First published:September 08, 2022
Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway has great potential to promote antitumor immunity. Development of activators for the cGAS-STING pathway (cGAS-STING activators) has profoundly revolutionized tumor immunotherapy. However, successful clinical application of cGAS-STING activators is contingent on having appropriate systems to achieve safe, effective, and specific delivery. There is an increasing emphasis on the design and application of nano drug delivery systems (NDDS) that can facilitate the delivery potential of cGAS-STING activators.

September 6, 2022

Science & Society

Lessons from COVID-19 to increase opioid vaccine acceptance

  • Roxana Damiescu,
  • Mita Banerjee,
  • Norbert W. Paul,
  • Thomas Efferth
First published:September 06, 2022
COVID-19 has put vaccine efficacy under a spotlight. However, the reluctance of people to be vaccinated has postponed the end of the COVID-19 pandemic. Currently, opioid vaccines are being developed, which could help prevent opioid addiction, overdoses, or relapse in combination with medication-assisted therapy. The fear is that the uptake of opioid vaccines could be met by the same reluctance as seen with COVID-19 vaccines.

August 31, 2022


Structural snapshot of a β-arrestin-biased receptor

  • Parishmita Sarma,
  • Ramanuj Banerjee,
  • Arun K. Shukla
First published:August 31, 2022
Atypical chemokine receptor subtype 3 (ACKR3), a chemokine receptor, couples selectively to β-arrestins (βarrs) but not to G proteins despite having seven transmembrane (7TM) helix architecture. Yen et al. present cryogenic-electron microscopy (cryo-EM) structures of agonist-bound ACKR3, elucidating a distinct chemokine-binding mechanism, and offering a structural template to probe the transducer-coupling bias at this receptor.

Commensal gut microbiota-based strategies for oral delivery of therapeutic proteins

  • Connie W. Woo,
  • Patrick Tso,
  • Jensen H.C. Yiu
First published:August 31, 2022
Open Access
Therapeutic proteins are rarely available in oral dosage form because the hostile environment of the human gastrointestinal (GI) tract and their large size make this delivery method difficult. Commensal bacteria in the gut face the same situation; however, they not only survive but low levels of their structural components such as lipopolysaccharide (LPS), peptidoglycan, and flagellin are also consistently detectable in the circulatory systems of healthy individuals. This opinion article discusses how gut bacteria survive in the gut, how their components penetrate the body from the perspective of the bacteria’s and the host’s proactivity, and how orally administered therapeutic proteins may be developed that exploit similar mechanisms to enter the body.

August 30, 2022


A pharmacological strategy to recapitulate exercise-induced antitumoral immunity

  • Amélie Rébillard,
  • Jacques A. Nunès,
  • Alice Carrier
First published:August 30, 2022
The antitumor activity of exercise by means of enhanced immune activation is documented, but better identification of the underlying mechanisms is required to develop new therapeutic strategies. Recent work from the Dr Bar-Sagi group reveals that exercise engages IL-15 signaling and pharmacological activation of the IL-15/IL-15R axis mimics the exercise-driven immune cell-mediated cytotoxicity in pancreatic cancer.

August 23, 2022


Targeting SARS-CoV-2 papain-like protease in the postvaccine era

  • Anh-Tien Ton,
  • Mohit Pandey,
  • Jason R. Smith,
  • Fuqiang Ban,
  • Michael Fernandez,
  • Artem Cherkasov
First published:August 23, 2022
While vaccines remain at the forefront of global healthcare responses, pioneering therapeutics against SARS-CoV-2 are expected to fill the gaps for waning immunity. Rapid development and approval of orally available direct-acting antivirals targeting crucial SARS-CoV-2 proteins marked the beginning of the era of small-molecule drugs for COVID-19. In that regard, the papain-like protease (PLpro) can be considered a major SARS-CoV-2 therapeutic target due to its dual biological role in suppressing host innate immune responses and in ensuring viral replication.

August 20, 2022


Odorant receptors as potential drug targets

  • Rafaella G. Naressi,
  • Deborah Schechtman,
  • Bettina Malnic
First published:August 20, 2022
Odorant receptors (ORs) belong to a large family of G protein-coupled receptors (GPCRs) that are highly expressed by olfactory sensory neurons of the nose. Accumulating evidence indicates that they are also expressed in a variety of nonolfactory tissues, which makes them new potential drug targets. Here we discuss the challenges and strategies to target these receptors.

August 16, 2022


GABA transport goes structural

  • Baruch I. Kanner,
  • Oshrat Dayan-Alon
First published:August 16, 2022
The γ-aminobutyric acid transporter 1 (GAT1) is a transporter which clears the inhibitory neurotransmitter γ-aminobutyric acid (GABA) from the synaptic cleft. The paper by Motiwala et al. documents a structure of GAT1 in complex with the antiepileptic drug tiagabine. This study will enable structure-based docking of large chemical libraries for the discovery of novel antiepileptics.

July 25, 2022

Feature Review

Mouse models of atherosclerosis in translational research

  • Iqra Ilyas,
  • Peter J. Little,
  • Zhiping Liu,
  • Yanyong Xu,
  • Danielle Kamato,
  • Bradford C. Berk,
  • Jianping Weng,
  • Suowen Xu
First published:July 25, 2022
Atherosclerotic cardiovascular disease (CVD), the major cause of premature human mortality, is a chronic and progressive metabolic and inflammatory disease in large- and medium-sized arteries. Mouse models are widely used to gain mechanistic insights into the pathogenesis of atherosclerosis and have facilitated the discovery of anti-atherosclerotic drugs. Despite promising preclinical studies, many drug candidates have not translated to clinical use because of the complexity of disease patho-mechanisms including lipid metabolic traits and inflammatory, genetic, and hemodynamic factors.

June 29, 2022


Biologics and cardiac disease: challenges and opportunities

  • Giulio Ciucci,
  • Andrea Colliva,
  • Roman Vuerich,
  • Giulio Pompilio,
  • Serena Zacchigna
First published:June 29, 2022
Open Access
Biologics are revolutionizing the treatment of chronic diseases, such as cancer and monogenic disorders, by overcoming the limits of classic therapeutic approaches using small molecules. However, the clinical use of biologics is limited for cardiovascular diseases (CVDs) , which are the primary cause of morbidity and mortality worldwide. Here, we review the state-of-the-art use of biologics for cardiac disorders and provide a framework for understanding why they still struggle to enter the field.

Current landscape of preclinical models of diabetic cardiomyopathy

  • Darnel Prakoso,
  • Miles J. De Blasio,
  • Mitchel Tate,
  • Rebecca H. Ritchie
First published:June 29, 2022
Patients with diabetes have an increased risk of developing heart failure, preceded by (often asymptomatic) cardiac abnormalities, collectively called diabetic cardiomyopathy (DC). Diabetic heart failure lacks effective treatment, remaining an urgent, unmet clinical need. Although structural and functional characteristics of the diabetic human heart are well defined, clinical studies lack the ability to pinpoint the specific mechanisms responsible for DC. Preclinical animal models represent a vital component for understanding disease aetiology, which is essential for the discovery of new targeted treatments for diabetes-induced heart failure.

April 7, 2022


Bringing lipidic lyotropic liquid crystal technology into biomedicine

  • Guillermo Blanco-Fernandez,
  • Barbara Blanco-Fernandez,
  • Anxo Fernández-Ferreiro,
  • Francisco Otero-Espinar
First published:April 07, 2022
Liquid crystals (LCs), discovered more than 130 years ago, are now emerging in the field of biomedicine. This article highlights the recent uses of lipid lyotropic LCs in therapeutics delivery, imaging, and tissue engineering and invites the scientific community to continue exploring the design of more complex LCs.