Related Experiment Video

Updated: Feb 27, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

Selumetinib for the treatment of non-small cell lung cancer

Francesca Casaluce1, Assunta Sgambato1, Paolo Maione1

  • 1a Division of Medical Oncology , 'S. G. Moscati' Hospital , Avellino , Italy.

Expert Opinion on Investigational Drugs
|July 5, 2017
PubMed
Abstract

Insights

KRAS mutations in non-small cell lung cancer (NSCLC) are common but lack effective targeted therapies. Combination therapies targeting the RAS-RAF-MEK-MAPK pathway show promise for future MEK inhibitor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • KRAS is the most frequent oncogene mutation in non-small cell lung cancer (NSCLC), affecting approximately one-third of patients.
  • Despite its prevalence, KRAS-mutant NSCLC remains largely 'undruggable' with no approved targeted therapies.
  • The clinical utility of KRAS mutations in NSCLC therapy is debated, limiting routine KRAS testing.

Purpose of the Study:

  • To review the current landscape of targeted therapies for KRAS-mutant NSCLC.
  • To evaluate the efficacy of MEK inhibitors, specifically selumetinib, in combination with docetaxel.
  • To discuss future strategies, including combination therapies and biomarker identification, for treating KRAS-mutant NSCLC.

Main Methods:

  • Review of a Phase II trial of selumetinib plus docetaxel versus docetaxel alone in KRAS-mutant NSCLC.
  • Analysis of a subsequent Phase III trial investigating the same combination therapy in advanced KRAS-mutant lung cancer.
  • Synthesis of expert opinion on current and future therapeutic approaches.

Main Results:

  • A Phase II trial demonstrated improved progression-free survival (PFS) and objective response rate (ORR) with selumetinib plus docetaxel.
  • A Phase III trial showed no significant improvement in survival or clinical benefit with the addition of selumetinib to docetaxel.
  • The combination therapy did not overcome the challenges associated with targeting KRAS-mutant NSCLC.

Conclusions:

  • Targeting KRAS-mutant NSCLC remains a significant challenge.
  • Combination therapies inhibiting the RAS-RAF-MEK-MAPK pathway are a promising strategy.
  • Identifying predictive biomarkers and understanding resistance mechanisms are crucial for advancing MEK inhibitor development in NSCLC.
Keywords:
KRASMEK-inhibitorsnon-small cell lung cancerselumetinibtargeted therapy

More Related Videos

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer04:04

Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer

Published on: February 12, 2017

11.1K
Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients07:43

Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients

Published on: September 25, 2018

11.1K

Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
596
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...
9.0K
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
508
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...
6.2K