Related Experiment Video

Updated: May 6, 2026

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

9.5K

Systematic review: Anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced

Issa J Dahabreh1, Teruhiko Terasawa, Peter J Castaldi

  • 1Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts 02111, USA.

Annals of Internal Medicine
|January 5, 2011
PubMed
Abstract

Insights

KRAS mutations in colorectal cancer patients treated with anti-EGFR antibodies are linked to worse survival outcomes. Wild-type KRAS status predicts better response to these therapies, highlighting its importance in treatment selection.

Area of Science:

  • Oncology
  • Genetics
  • Clinical Trials

Background:

  • KRAS mutations are investigated as predictive biomarkers for advanced colorectal cancer (CRC) treatment.
  • Anti-epidermal growth factor receptor (EGFR) antibodies like cetuximab and panitumumab are used in CRC therapy.

Purpose of the Study:

  • To determine if KRAS mutation status affects anti-EGFR therapy outcomes in advanced CRC.
  • To assess if KRAS status predicts clinical outcomes in patients receiving anti-EGFR treatments.

Main Methods:

  • Searched MEDLINE and genetics databases for observational studies (up to March 2010).
  • Searched major trial registries for randomized controlled trials (up to September 2010).
  • Included studies assessing KRAS mutations as predictors of survival and treatment failure in metastatic CRC patients receiving anti-EGFR therapy.

Main Results:

  • No significant survival benefit from anti-EGFR therapy in KRAS-mutated patients (HR, 1.0).
  • Evidence favors anti-EGFR therapy in KRAS wild-type patients, with improved overall survival (HR, 1.30) and progression-free survival (HR, 2.22).
  • Meta-analysis showed KRAS mutations have 49% sensitivity and 93% specificity in predicting lack of response.

Conclusions:

  • KRAS mutations are consistently linked to poorer survival and higher treatment failure rates in advanced CRC patients on anti-EGFR therapy.
  • Limited evidence from randomized studies necessitates patient-level data to fully understand mutation-treatment interactions.
  • Publication bias may be a concern, and further research is needed.

More Related Videos

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.4K
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

8.0K

Related Concept Videos

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...
6.4K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
5.7K
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...
3.6K
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...
7.1K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
84