関連する実験動画

Updated: Sep 9, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

EGFR変異性肺がんにおけるオシメルチニブ獲得耐性を克服するためのMK3/c- Myc相互作用を標的とする

Zhen Chen¹, Karin A Vallega¹, Dongsheng Wang¹

¹Departments of Hematology and Medical Oncology and Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, USA.

|August 31, 2025

まとめ

EGFR変異性肺がんにおけるオシメルチニブの有効性には,c- Mycを標的とする事が重要だ. MKK3/ c- MycとSGI-1027の相互作用を妨害することで,c- Mycのレベルを低下させ,アポトーシスを強化することで抵抗を克服します.

科学分野:

腫瘍学
分子生物学
薬物の発見

背景:

EGFR変異性非小細胞肺がん (NSCLC) のオシメルチニブ耐性は臨床的な課題である.
c- Mycの阻害はオシメルチニブの有効性にとって不可欠であるが,特定の阻害剤は存在しない.
c- MycとMK3のレベルが上昇し,MK3/ c- Mycの相互作用が増加すると,オシメルチニブ耐性細胞が特徴づけられる.

研究の目的:

EGFR変異性NSCLCにおけるオシメルチニブ耐性を克服する戦略としてMK3/ c- Myc相互作用をターゲットにすることを調査する.
新型MK3/ c- Myc相互作用破壊剤であるSGI-1027とオシメルチニブとの併用による有効性を評価する.

主な方法:

オシメルチニブ耐性EGFR変異性NSCLCの細胞系とマウスモデルを使用した.
MKK3/c-Mycの相互作用を妨害し,c-Mycの分解を促進するためにSGI-1027を使用しています.
細胞活性,アポプトーシス,腫瘍増殖抑制を評価した.

主要な成果:

SGI- 1027は,MK3/ c- Mycの相互作用を妨害し,分解を促進することによって,c- Mycのレベルを低下させた.
オシメルチニブとSGI- 1027の併用療法により,細胞生存率が低下し,耐性細胞のアポトーシスが増加しました.
SGI- 1027とオシメルチニブを併用した薬は,単体薬よりも腫瘍の成長を効果的に抑制した.

結論:

EGFR変異性NSCLCにおけるオシメルチニブ耐性を克服するための有効な戦略は,MK3/ c- Myc相互作用を妨害することです.
オシメルチニブ自体は,敏感な細胞におけるMK3/ c- Mycの相互作用を阻害することによって,c- Mycの分解を誘導する可能性があります.
この研究は,c-Mycの調節メカニズムを明らかにし,耐性NSCLCに対する新しい治療アプローチを提供します.

キーワード:

獲得した抵抗性 MKK3 と肺がんオシメルチニブ c-マイク

さらに関連する動画

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

関連する概念動画

Mitogens and the Cell Cycle

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...

Targeted Cancer Therapies

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...

Treatment Resistant Cancers

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...

mTOR Signaling and Cancer Progression

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...

Abnormal Proliferation

Abnormal Proliferation

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...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...