Related Experiment Video

Updated: Sep 2, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

8.9K

Co-targeting of specific epigenetic regulators in combination with CDC7 potently inhibit melanoma growth

Suresh Chava1, Suresh Bugide1, Parmanand Malvi1

  • 1Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL 35233, USA.

Iscience
|August 9, 2022
PubMed

Insights

Targeting cell division cycle 7 (CDC7) kinase, overexpressed in melanoma, inhibits tumor growth and metastasis. Combining CDC7 inhibition with epigenetic drugs like GSK343 or OF1 enhances anti-melanoma effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Melanoma is an aggressive skin cancer with frequent metastasis.
  • Current therapies offer limited benefit to some melanoma patients.
  • The role of cell division cycle 7 (CDC7) kinase in melanoma progression is not fully understood.

Purpose of the Study:

  • To investigate the role of CDC7 in melanoma.
  • To evaluate CDC7 inhibition as a therapeutic strategy for melanoma.
  • To identify potential combination therapies for melanoma targeting CDC7.

Main Methods:

  • Assessed CDC7 expression in melanoma patient samples.
  • Utilized a chemical genetics screen with epigenetic inhibitors (GSK343, OF1).
  • Investigated the effects of CDC7 inhibition on cell cycle, senescence, apoptosis, tumor growth, and metastasis.

Main Results:

  • CDC7 is overexpressed in melanoma, correlating with shorter patient survival.
  • CDC7 inhibition induces cell cycle arrest, senescence, and apoptosis, suppressing melanoma growth and metastasis.
  • Combination of CDC7 inhibitor XL413 with EZH2 inhibitor GSK343 or BRPF1/2/3 inhibitor OF1 demonstrated synergistic anti-melanoma effects.
  • Combined treatment upregulated tumor-suppressive genes, leading to increased apoptosis.

Conclusions:

  • CDC7 is a key driver of melanoma tumor growth and metastasis.
  • Targeting CDC7 alone or in combination with EZH2 or BRPF1/2/3 inhibitors is a promising therapeutic strategy for melanoma.
Keywords:
CancerCell biologyChemistryEpigenetics

More Related Videos

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

2.5K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.4K

Related Concept Videos

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...
7.8K
Mitogens and the Cell Cycle02:38

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...
6.6K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
Combination Therapies and Personalized Medicine02:50

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...
5.1K
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...
5.7K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
650