Related Experiment Video

Updated: Dec 31, 2025

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

19.1K

Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway

Kari J Kurppa1, Yao Liu2, Ciric To1

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.

Cancer Cell
|January 15, 2020
PubMed

Insights

Targeting dormant cancer cells after EGFR TKI treatment is key. Combining EGFR/MEK inhibition with YAP/TEAD blockade overcomes dormancy by promoting apoptosis in non-small cell lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Tumor dormancy following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant non-small cell lung cancer (NSCLC) presents a significant therapeutic challenge.
  • Understanding the mechanisms that drive this dormancy is crucial for developing effective eradication strategies.

Purpose of the Study:

  • To investigate the mechanisms underlying tumor cell dormancy after EGFR TKI treatment.
  • To identify novel therapeutic targets for eradicating dormant cells and overcoming treatment resistance in NSCLC.

Main Methods:

  • Utilized combined EGFR/MEK inhibition to block ERK1/2 reactivation and uncover dormant cells.
  • Characterized the senescence-like dormant state, focusing on YAP/TEAD activity and its interaction with SLUG.
  • Assessed the impact of pharmacological YAP/TEAD co-inhibition and genetic YAP1 deletion on dormant cell depletion.

Main Results:

  • Combined EGFR/MEK inhibition induced a senescence-like dormant state characterized by high YAP/TEAD activity.
  • YAP/TEAD, via SLUG, represses the pro-apoptotic protein BMF, thereby limiting drug-induced apoptosis.
  • Pharmacological co-inhibition of YAP/TEAD or genetic YAP1 deletion effectively depleted dormant cells by enhancing apoptosis.

Conclusions:

  • Targeting the YAP/TEAD pathway in conjunction with EGFR/MEK inhibition offers a promising strategy to eradicate dormant non-small cell lung cancer cells.
  • Enhancing the initial efficacy of targeted therapies by overcoming dormancy could lead to improved and prolonged treatment responses in cancer patients.
Keywords:
YAPdormancydrug resistancedrug toleranceepidermal growth factor receptorlung cancersenescence

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.3K
Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

11.4K

Related Concept Videos

Abnormal Proliferation02:23

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...
5.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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...
8.1K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
7.9K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
13.7K
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...
4.5K