Related Experiment Video

Updated: Dec 13, 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

8.2K

Should we keep rocking? Portraits from targeting Rho kinases in cancer

Graziella Ribeiro de Sousa1, Gabriela Maciel Vieira1, Pablo Ferreira das Chagas1

  • 1Ribeirão Preto Medical School, University of São Paulo, Brazil.

Pharmacological Research
|July 30, 2020
PubMed

Insights

Rho-associated coiled-coil kinases (ROCK1 and ROCK2) are promising cancer drug targets. However, ROCK inhibition may paradoxically promote cancer spread and metastasis, posing risks in clinical applications.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Rho-associated coiled-coil kinases (ROCK1 and ROCK2) regulate cytoskeleton and are implicated in cancer metastasis.
  • ROCK dysregulation correlates with poorer survival in various cancers, making them attractive therapeutic targets.

Purpose of the Study:

  • To review ROCK functions, roles in adult and pediatric cancers, and prognostic value.
  • To summarize advances in ROCK pharmacological inhibition and discuss potential detrimental effects.

Main Methods:

  • Literature review of ROCK functions, cancer roles, prognostic significance, and therapeutic strategies.
  • Analysis of pre-clinical and clinical data on ROCK inhibitors.
  • Discussion of off-target effects and pro-survival impacts of ROCK inhibition.

Main Results:

  • ROCKs are crucial for cancer metastasis and survival, with controversial prognostic roles in pediatric cancers.
  • Pharmacological inhibition of ROCKs shows promise in pre-clinical models but presents significant challenges.
  • ROCK inhibition can promote cancer stem cell survival, dormancy, and dissemination, alongside context-dependent adverse effects.

Conclusions:

  • ROCK inhibitors offer potential for cancer therapy but require careful consideration of risks.
  • Detrimental effects like enhanced metastasis and resistance necessitate further research for safe and effective anti-ROCK strategies.
  • Understanding ROCKs' complex roles is critical for developing novel cancer treatments, especially in pediatric oncology.
Keywords:
AR-12286 (Pubchem CID: 66906051)AT13148 (Pubchem CID: 24905401)Ewing’s sarcomaFasudil (Pubchem CID: 3547)H-1152 (Pubchem CID: 448043)LX7101 (Pubchem CID: 56962369)OsteosarcomaPediatric tumorRKI-1447 (Pubchem CID: 60138149)ROCKRipasudil (Pubchem CID: 9863672)Wilm’s tumorY-27632Y-27632 (Pubchem CID: 448042)Y-33075 (Pubchem CID: 9810884)YM529 (Pubchem CID: 130956)

More Related Videos

RhoC GTPase Activation Assay09:58

RhoC GTPase Activation Assay

Published on: August 22, 2010

12.9K
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.4K

Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.0K
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
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...
8.5K
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 Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.9K
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...
5.0K