Related Experiment Video

Updated: Dec 17, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

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

9.1K

Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours

João M Fernandes Neto1, Ernest Nadal2, Evert Bosdriesz1,3

  • 1Division of Molecular Carcinogenesis and Oncode Institute. The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Nature Communications
|June 24, 2020
PubMed

Insights

Multiple Low Dose (MLD) therapy uses low drug doses to block cancer growth without resistance. This approach shows promise for treating EGFR mutant non-small cell lung cancer (NSCLC) and overcoming acquired resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Targeted cancer drug resistance often arises from high drug doses creating selective pressure.
  • Alternative therapeutic strategies are needed to overcome resistance in oncogenic signaling pathways.

Purpose of the Study:

  • To investigate the efficacy of a Multiple Low Dose (MLD) therapy model in EGFR-mutant non-small cell lung cancer (NSCLC).
  • To determine if MLD therapy can prevent the development of drug resistance.

Main Methods:

  • Testing MLD therapy in 3D (RAF + MEK + ERK) and 4D (EGFR + RAF + MEK + ERK) inhibitor combinations.
  • Evaluating MAPK signaling, proliferation, and resistance development in EGFR-mutant NSCLC cells.
  • Assessing durable responses and toxicity in preclinical animal models.

Main Results:

  • As little as 20% of individual effective drug doses in MLD combinations completely blocked MAPK signaling and proliferation.
  • EGFR-mutant NSCLC cells treated with MLD therapy did not develop resistance.
  • MLD therapy demonstrated durable responses without significant toxicity in animal models.

Conclusions:

  • MLD therapy is a potential strategy to inhibit oncogenic signaling pathways effectively.
  • This approach may prevent resistance development and offer clinical benefit for NSCLC patients, including those resistant to current therapies.

More Related Videos

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.5K
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.3K

Related Concept Videos

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...
8.5K
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...
5.8K
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...
7.6K
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
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
9.7K