Dpep, a Cell-Penetrating Peptide Targeting ATF5, CEBPB and CEBPD, Synergistically Combines with ABT-263 and

Qing Zhou1, Trang Thi Thu Nguyen1,2, James M Angelastro3

  • 1Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.

Cells
|May 13, 2026
PubMed

Insights

The cell-penetrating peptide Dpep, combined with ABT-263 or decitabine, synergistically inhibits diverse cancer cell growth, even overcoming Dpep resistance. Combinations demonstrate significant therapeutic potential in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Dpep is a cell-penetrating peptide targeting transcription factors ATF5, CEBPB, and CEBPD, showing selective tumor cell suppression and potential as a cancer therapeutic.
  • Investigating Dpep combinations is crucial for enhancing efficacy and overcoming potential peptide resistance in cancer treatment.

Purpose of the Study:

  • To assess the synergistic efficacy of Dpep in combination with ABT-263 (BCL2 inhibitor) and decitabine (hypomethylating agent).
  • To evaluate the effectiveness of these combinations against Dpep-resistant cancer cell lines.
  • To determine the therapeutic potential of Dpep combinations in vivo using a melanoma xenograft model.

Main Methods:

  • Combination studies of Dpep with ABT-263 and decitabine in various solid and liquid tumor cell types in vitro.
  • Assessment of combination efficacy in Dpep-resistant cell lines selected in vitro and in vivo.
  • In vivo efficacy testing of Dpep and ABT-263 combination in a mouse melanoma xenograft model.

Main Results:

  • Dpep combined with ABT-263 or decitabine synergistically suppressed the growth of diverse tumor cell types.
  • The combinations effectively inhibited Dpep-resistant cell lines, indicating a strategy to overcome resistance.
  • In a mouse melanoma model, the Dpep and ABT-263 combination significantly inhibited tumor growth and achieved a 40% durable survival rate.

Conclusions:

  • Dpep combinations with ABT-263 and decitabine show significant synergistic anti-cancer activity.
  • These combinations hold promise for overcoming Dpep resistance and represent potential therapeutic strategies for various cancers.
  • Further development of Dpep in combination therapies is warranted based on these preclinical findings.

Related Concept Videos

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...
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 specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...