Related Experiment Video

Updated: Dec 2, 2025

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

6.8K

Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A

Kasturi Ranganna1, Chelliah Selvam1, Amruthesh Shivachar1

  • 1Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St., Houston, TX 77004, USA.

International Journal of Molecular Sciences
|November 5, 2020
PubMed

Insights

Histone deacetylase inhibitors (HDACIs) offer new cancer treatment avenues by targeting epigenetic changes. Combining HDAC and PI3K pathway inhibition shows promise, leading to the development of single hybrid molecules for enhanced efficacy.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Carcinogenesis is triggered by genetic mutations and epigenetic alterations.
  • Histone deacetylases (HDACs) are key epigenetic modifiers implicated in various diseases, especially cancers.
  • Dysregulation of the PI3K signaling pathway is also common in human cancers.

Purpose of the Study:

  • To review the role of HDACs in cancer.
  • To explore HDAC inhibitors (HDACIs) as epigenetic therapeutics.
  • To examine HDAC-based strategies targeting the PI3K pathway for cancer treatment.

Main Methods:

  • Literature review of HDACs, epigenetic alterations, and PI3K pathway in cancer.
  • Analysis of HDACIs as single agents and in combination therapies.
  • Discussion of polypharmacology strategies for developing hybrid HDAC-PI3K molecules.

Main Results:

  • HDACIs show therapeutic promise in hematological, solid malignancies, and non-neoplastic diseases.
  • Single-agent HDACIs can inhibit both HDAC and PI3K pathways, but resistance can occur.
  • Combined inhibition of HDACs and PI3Ks demonstrates synergistic efficacy.

Conclusions:

  • Targeted inhibition of HDACs and PI3K pathways offers a promising therapeutic strategy.
  • The development of single HDAC-PI3K hybrid molecules via polypharmacology is a key advancement.
  • HDAC-based epigenetic approaches targeting the PI3K pathway represent a significant evolution in cancer therapy.
Keywords:
CUDC-907HDAC-PI3K hybrid moleculeepigeneticshistone deacetylasehistone deacetylase inhibitorsphosphatidylinositol kinase

More Related Videos

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

8.8K
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.5K

Related Concept Videos

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...
4.9K
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...
8.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.7K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.4K
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...
5.7K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.5K