Related Experiment Video

Updated: Jan 26, 2026

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
07:55

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma

Published on: April 11, 2018

14.9K

Combination of eribulin plus AKT inhibitor evokes synergistic cytotoxicity in soft tissue sarcoma cells

Naotaka Hayasaka1, Kohichi Takada2,3, Hajime Nakamura1

  • 1Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Scientific Reports
|April 10, 2019
PubMed

Insights

The AKT pathway drives soft tissue sarcoma (STS) progression. Combining eribulin with an AKT inhibitor, MK-2206, overcomes eribulin resistance by inducing cell cycle arrest and apoptosis in STS cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Activated AKT signaling is implicated in soft tissue sarcoma (STS) pathogenesis.
  • Elevated phosphorylated AKT (p-AKT) levels correlate with poor prognosis in some STS cases.
  • Eribulin, a microtubule inhibitor, shows efficacy in advanced liposarcoma and breast cancer, but resistance mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of AKT signaling in eribulin resistance in STS.
  • To evaluate the efficacy of combining eribulin with an AKT inhibitor (MK-2206) for STS treatment.

Main Methods:

  • Assessed p-AKT levels in STS cells and correlated them with eribulin resistance.
  • Evaluated the synergistic effect of eribulin and MK-2206 on STS cell growth in vitro and in vivo.
  • Investigated the molecular mechanisms underlying the combination therapy's effects, including cell cycle regulation and apoptosis.

Main Results:

  • Increased p-AKT levels were associated with eribulin resistance in STS cells.
  • The combination of eribulin and MK-2206 synergistically inhibited STS cell growth.
  • Combined treatment induced G1/G2/M cell cycle arrest and caspase-dependent apoptosis.

Conclusions:

  • p-AKT signaling is significant in mediating eribulin resistance in STS.
  • Combining eribulin with an AKT inhibitor offers a potential therapeutic strategy for STS patients.
  • This combination warrants further clinical development for STS treatment.

More Related Videos

A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies07:15

A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies

Published on: July 28, 2020

10.3K
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

9.8K

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.9K
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...
5.4K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.6K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.3K
Plant Cells and Tissues02:01

Plant Cells and Tissues

Plant tissues are collections of similar cells performing related functions. Different plant tissues will have their own specialized roles and can be combined with other tissues to form organs such as flowers, fruit, stem, and leaves. Two major types of plant tissue include meristematic and permanent tissue.
65.5K
Lymphoid Cells and Tissues01:18

Lymphoid Cells and Tissues

Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
3.0K