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

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.4K
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...
3.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

4.7K
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...
4.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.8K
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...
3.8K
Abnormal Proliferation02:23

Abnormal Proliferation

4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
The Ras Gene02:38

The Ras Gene

6.2K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

8.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K

You might also read

Related Articles

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

Sort by
Same author

CDK2 Inhibition Exerts RB-Independent Antitumor Activity in CDK4/6 Inhibitor-Resistant HR+/HER2- Breast Cancer.

Cancer research·2026
Same author

Evaluation of the Current ATTR-CM Treatment Landscape via a Mathematical Model of TTR Dissociation and Amyloid Formation.

CPT: pharmacometrics & systems pharmacology·2026
Same author

Comparing civil legal actions among international and Canadian or American medical graduates in Canada: a retrospective cohort study.

BMJ open·2026
Same author

NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Dual inhibition of GTP-bound (ON) and GDP-bound (OFF) KRAS<sup>G12C</sup> suppresses PI3Kα and leads to potent tumor inhibition.

bioRxiv : the preprint server for biology·2026
Same author

Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.

The Biochemical journal·2026
Same journal

Erratum for the Research Article "Detecting supramolecular organic nanoparticles during heat wave".

Science (New York, N.Y.)·2026
Same journal

Local signals, systemic decline.

Science (New York, N.Y.)·2026
Same journal

The mechanics of liver regeneration.

Science (New York, N.Y.)·2026
Same journal

Computing in a memory with physics.

Science (New York, N.Y.)·2026
Same journal

Retraction.

Science (New York, N.Y.)·2026
Same journal

Making time.

Science (New York, N.Y.)·2026
See all related articles

Related Experiment Video

Updated: Jun 14, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K

BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction.

Dhirendra K Simanshu1, Rui Xu2, James P Stice2

  • 1National Cancer Institute (NCI) RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.

Science (New York, N.Y.)
|June 12, 2025
PubMed
Summary
This summary is machine-generated.

BBO-10203 is a novel oral drug targeting phosphoinositide 3-kinase α (PI3Kα), showing significant tumor inhibition in preclinical models. This PI3Kα inhibitor effectively reduces tumor growth without causing hyperglycemia.

More Related Videos

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

1.5K
Studying TGF-&#946; Signaling and TGF-&#946;-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

Related Experiment Videos

Last Updated: Jun 14, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K
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

1.5K
Studying TGF-&#946; Signaling and TGF-&#946;-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Phosphoinositide 3-kinase α (PI3Kα) is a key signaling enzyme implicated in various cancers.
  • RAS-mediated activation of PI3Kα plays a crucial role in tumor development and progression.
  • Oncogenic mutations in PIK3CA, KRAS, and HER2 amplification/overexpression are common drivers in multiple tumor types.

Purpose of the Study:

  • To evaluate the efficacy of BBO-10203, an orally available PI3Kα inhibitor, in preclinical cancer models.
  • To investigate the mechanism of action of BBO-10203, focusing on its specific binding to the RAS-binding domain of PI3Kα.
  • To assess the potential of BBO-10203 as a monotherapy and in combination with other targeted agents.

Main Methods:

  • BBO-10203 was administered orally in preclinical cancer models.
  • Inhibition of PI3Kα activation was assessed in tumors with specific oncogenic mutations or amplifications.
  • Tumor growth inhibition was evaluated in various tumor types, including those with KEAP1 and STK11 mutations.
  • Combination therapies included inhibitors of CDK4/6, ER, HER2, and KRAS-G12C.

Main Results:

  • BBO-10203 covalently and specifically binds to the RAS-binding domain of PI3Kα, preventing its activation by RAS proteins.
  • The drug demonstrated PI3Kα inhibition in tumors with oncogenic KRAS, PIK3CA mutations, or HER2 amplification/overexpression.
  • Significant tumor growth inhibition was observed across multiple tumor types.
  • Enhanced efficacy was noted in combination therapies, particularly in tumors with KEAP1 and STK11 mutations.

Conclusions:

  • BBO-10203 is a potent PI3Kα inhibitor with broad antitumor activity in preclinical models.
  • The drug's efficacy is enhanced when combined with other targeted therapies, including CDK4/6, ER, HER2, and KRAS-G12C inhibitors.
  • BBO-10203 achieves antitumor effects without inducing hyperglycemia, suggesting a distinct therapeutic window.