Related Experiment Video

Updated: May 25, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors

Yanjie Zhang1, X F Steven Zheng

  • 1Cancer Institute of New Jersey and Department of Pharmacology, University of Medicine & Dentistry New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, USA.

Cell Cycle (Georgetown, Tex.)
|January 21, 2012
PubMed

Insights

New ATP-competitive mTOR kinase inhibitors (mTorKIs) show potent anticancer activity against colorectal cancer (CRC), even in resistant cells. Intrinsic resistance and mTOR-independent 4E-BP1 phosphorylation were identified as key factors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • ATP-competitive mTOR kinase inhibitors (mTorKIs) represent a novel class of mTOR-targeted agents.
  • mTorKIs exhibit enhanced anticancer potency compared to rapamycin in preclinical models.
  • Understanding sensitivity and resistance mechanisms to mTorKIs in cancer is crucial.

Purpose of the Study:

  • To evaluate the efficacy of mTorKIs across a diverse panel of colorectal cancer (CRC) cell lines.
  • To investigate the potential of mTorKIs in treating CRCs resistant to other therapies, such as EGFR inhibitors.
  • To identify biomarkers predicting sensitivity or resistance to mTorKIs.

Main Methods:

  • Screening of a large panel of colorectal cancer cell lines with mTorKIs.
  • Analysis of CRC cell lines harboring K-Ras or B-Raf mutations.
  • Investigation of mTOR-independent 4E-BP1 phosphorylation as a resistance marker.

Main Results:

  • mTorKIs demonstrated broader anti-CRC activity than rapamycin, including in cells with K-Ras/B-Raf mutations.
  • A significant proportion (40%) of CRC cell lines exhibited intrinsic resistance to mTorKIs.
  • mTOR-independent 4E-BP1 phosphorylation was correlated with mTorKI resistance.

Conclusions:

  • mTorKIs show promising preclinical efficacy for human CRC clinical trials.
  • Intrinsic drug resistance to mTorKIs is prevalent in cancer cells.
  • 4E-BP1 phosphorylation serves as a potential predictive biomarker for mTorKI response.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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

PI3K/mTOR/AKT Signaling Pathway

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 rapamycin-insensitive companion...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...