Related Experiment Video

Updated: Jun 4, 2025

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

7.9K

ACK1/TNK2 kinase: molecular mechanisms and emerging cancer therapeutics

Dhivya Sridaran1, Nupam P Mahajan2

  • 1Division of Urologic Surgery, Department of Surgery, Washington University at St. Louis, St. Louis, MO 63110, USA.

Trends in Pharmacological Sciences
|December 25, 2024
PubMed

Insights

Activated CDC42-associated kinase 1 (ACK1) is an oncokinase driving cancer progression and epigenetic regulation. New research highlights its immunomodulatory roles and promising small-molecule inhibitors advancing toward clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Activated CDC42-associated kinase 1 (ACK1), encoded by the TNK2 gene, is a cytoplasmic non-receptor tyrosine kinase.
  • Aberrant ACK1 activation is linked to increased cancer severity and progression across multiple malignancies.
  • ACK1 functions as an epigenetic regulator, contributing to tumor development.

Purpose of the Study:

  • To summarize recent advancements in understanding ACK1 regulation and signaling pathways.
  • To elucidate the immunomodulatory functions of ACK1, particularly in T cell activation.
  • To review preclinical data on small-molecule inhibitors targeting ACK1 for cancer therapy.

Main Methods:

  • Literature review of recent research on ACK1.
  • Analysis of studies on ACK1's role in epigenetic regulation and cancer progression.
  • Overview of preclinical data for ACK1-targeting small-molecule inhibitors.

Main Results:

  • ACK1's critical role in driving cancer progression through epigenetic mechanisms is confirmed.
  • ACK1 influences T cell activation, suggesting a role in cancer immunity.
  • Several potent ACK1-targeting small-molecule inhibitors have shown promise in preclinical studies.

Conclusions:

  • ACK1 is a significant oncokinase and epigenetic regulator with therapeutic potential.
  • Understanding ACK1's signaling and immunomodulatory roles is crucial for developing effective cancer treatments.
  • Promising ACK1 inhibitors are progressing towards clinical trials, offering new therapeutic avenues for cancer patients.
Keywords:
ACK1T cellsTNK2cancersepigeneticsimmune modulationkinase inhibitors

More Related Videos

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

7.3K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

14.8K

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...
3.7K
Targeted Cancer Therapies02:57

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...
7.4K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.3K
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...
3.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K