Related Experiment Video

Updated: Dec 27, 2025

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

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

Published on: December 7, 2014

15.1K

Vorinostat in patients with resistant BRAF mutated advanced melanoma: a proof of concept study

Sanne Huijberts1, Liqin Wang2, Rodrigo Leite de Oliveira2

  • 1Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.

Future Oncology (London, England)
|March 4, 2020
PubMed

Insights

Sequential treatment with vorinostat and BRAF/MEK inhibitors shows promise for overcoming resistance in BRAF-mutant melanoma. This approach targets secondary mutations that cause treatment resistance, potentially improving patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • BRAF- and MEK-inhibitors (BRAFi/MEKi) offer clinical benefit in BRAF-mutant melanoma but are limited by acquired resistance.
  • Secondary mutations in the MAPK pathway are a key mechanism of resistance to BRAFi/MEKi therapy.

Purpose of the Study:

  • To evaluate the efficacy of sequential treatment with vorinostat (an HDAC inhibitor) and BRAFi/MEKi in patients with resistant BRAF-mutant melanoma.
  • To demonstrate anti-tumor response in progressive lesions using RECIST 1.1 criteria.

Main Methods:

  • This proof-of-concept study involves sequential administration of vorinostat and BRAFi/MEKi.
  • Detection of resistant clones with secondary mutations in circulating tumor DNA (ctDNA).
  • Pharmacokinetic, pharmacodynamic, and pharmacogenetic analyses are included as exploratory endpoints.

Main Results:

  • The study aims to demonstrate tumor response and the purging of resistant clones by vorinostat treatment.
  • Secondary mutations in ctDNA will be monitored to assess treatment impact on resistant clones.

Conclusions:

  • Sequential treatment with vorinostat may overcome BRAFi/MEKi resistance in melanoma by targeting secondary mutations.
  • This strategy holds potential for improving therapeutic outcomes in resistant melanoma patients.
Keywords:
BRAF inhibitorBRAFV600E mutationMEK inhibitorhistone deacetylase inhibitormelanomametastaticresistance

More Related Videos

A Melanoma Patient-Derived Xenograft Model07:07

A Melanoma Patient-Derived Xenograft Model

Published on: May 20, 2019

13.0K
Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma08:18

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma

Published on: September 8, 2021

3.3K

Related Concept Videos

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...
3.6K
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...
8.6K
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...
5.1K