Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

5.6K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

7.2K
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...
7.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

8.6K
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...
8.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

5.4K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.4K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

8.3K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Integrating antibody-drug conjugates into solid tumor oncology: Current standards and future directions.

Cancer·2026
Same author

Lymph node stromal topology as a hidden regulator of breast cancer outcome: commentary on reticular network analysis<sup>†</sup>.

The Journal of pathology·2026
Same author

Therapy Optimization in mHSPC: Insights from a Multidisciplinary Uro-Oncology Expert Panel.

Advances in therapy·2026
Same author

Differentiating Upper Tract Urothelial Carcinoma with Synchronous or Metachronous Bladder Cancer.

Current issues in molecular biology·2026
Same author

Health-related quality of life in breast cancer measured with EQ-5D-5L.

Journal of patient-reported outcomes·2026
Same author

Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis.

Nature communications·2026

Related Experiment Video

Updated: Jan 18, 2026

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.3K

RANK Pathway Inhibition Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibitors and Enhances Immune Response.

Inês Gomes1, Maria Martelo1, Rúben D Vilela1

  • 1Oncology Translational Laboratory, GIMM - Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal.

Molecular Cancer Therapeutics
|May 30, 2025
PubMed
Summary
This summary is machine-generated.

Combining cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with receptor activator of nuclear factor κB ligand inhibitors (RANKLi) shows promise for treating triple-negative breast cancer (TNBC). This novel therapeutic strategy enhances cell cycle arrest and elicits an antitumor immune response.

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.5K
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
13:19

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

3.8K

Related Experiment Videos

Last Updated: Jan 18, 2026

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.3K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.5K
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
13:19

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

3.8K

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Chemotherapy is the primary treatment for triple-negative breast cancer (TNBC), despite limitations.
  • Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are effective in luminal breast cancer but not TNBC.
  • Receptor activator of nuclear factor κB (RANK) pathway activation correlates with poor prognosis in TNBC and CDK4/6i resistance.

Purpose of the Study:

  • To investigate the therapeutic potential of combining CDK4/6i with RANK ligand inhibitors (RANKLi) in TNBC.
  • To analyze the effect of RANK inhibition on TNBC response to CDK4/6i in vitro and in vivo.
  • To evaluate the immunomodulatory effects of this combination therapy.

Main Methods:

  • In vitro analysis of RANK knockdown or RANKLi in pRB-proficient TNBC cells treated with CDK4/6i.
  • In vivo assessment of CDK4/6i + RANKLi efficacy using patient-derived and cell line-derived xenograft models.
  • Analysis of tumor immune microenvironment alterations in syngeneic TNBC and luminal breast cancer models.

Main Results:

  • RANK knockdown or RANKLi sensitized pRB-proficient TNBC cells to CDK4/6i in vitro.
  • The combination of palbociclib (a CDK4/6i) and RANKLi inhibited tumor growth and metastasis in vivo.
  • Therapy enhanced cell cycle arrest and promoted an antitumor immune response, increasing CD4+ and CD8+ T cells while decreasing tumor-associated macrophages.

Conclusions:

  • Combining CDK4/6i and RANKLi represents a potential new therapeutic strategy for pRB-proficient TNBC.
  • This combination therapy demonstrates significant anti-tumor efficacy and immunomodulatory benefits.
  • The findings suggest broader applicability across breast cancer subtypes.