Related Experiment Video

Updated: May 21, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional

Xia Zhou1, Bilin Tan2, Tingting Zhang2,1

  • 1Department of Heart Disease of Traditional Chinese Medicine, Zigong First People's Hospital, Zigong, 643000, China.

Cellular Oncology (Dordrecht, Netherlands)
|May 20, 2026
PubMed

Insights

G protein-coupled receptors (GPCRs) are key in tumors but context-dependent. New multi-dimensional strategies are needed to overcome limitations of current cancer therapies targeting GPCRs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are crucial in tumor signaling and microenvironment regulation.
  • GPCR functions are highly context-dependent within the heterogeneous tumor microenvironment (TME).
  • Conventional single-axis inhibition strategies are limited due to complex, multidimensional GPCR regulation in cancer.

Purpose of the Study:

  • To systematically examine tumor-associated GPCR distribution and functions.
  • To critically analyze the failure of current cancer therapies in the TME context.
  • To spotlight next-generation strategies for context-aware TME modulation.

Main Methods:

  • Systematic review of GPCR distribution and pathological functions in tumors.
  • Critical analysis of existing therapeutic modalities' limitations in the TME.
  • Exploration of novel therapeutic strategies including allosteric modulation, targeted protein degradation, nucleic acid therapeutics, and engineered cell therapies.

Main Results:

  • GPCRs exhibit context-dependent roles, driving proliferation and immunosuppression simultaneously.
  • Current therapies often fail due to parallel pathway reactivation and complex TME interactions.
  • Next-generation strategies offer potential for context-aware, multi-dimensional TME modulation.

Conclusions:

  • A paradigm shift from single-axis inhibition to multi-dimensional regulation of GPCRs is necessary for durable cancer therapies.
  • Integrating advanced technologies like AI, cryo-EM, and organoids will drive this transformation.
  • Next-generation GPCR-targeted therapies hold promise for actively modulating the TME for improved cancer treatment outcomes.
Keywords:
Allosteric modulationGPCR targetingIntelligent frontiersMultidimensional cancer therapeuticsSignal transduction mechanismsTargeted protein degradation

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Related Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...