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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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...
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Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

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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...
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Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

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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.
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Cancer Therapies02:49

Cancer Therapies

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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...
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Treatment Resistant Cancers02:56

Treatment Resistant Cancers

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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...
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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Rapidly evolving therapeutic advances for classical EGFR-mutant NSCLC.

Kelsey Pan1, Suresh S Ramalingam1

  • 1Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, GA, United States.

Frontiers in Oncology
|December 24, 2025
PubMed
Summary

Precision oncology for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) shows promise, but resistance to tyrosine kinase inhibitors (TKIs) persists. New combination strategies and resistance-targeting therapies are advancing treatment for NSCLC.

Keywords:
ADCEGFRNSCLCosimertinibtargeted therapy

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

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Area of Science:

  • Oncology
  • Precision Medicine
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has seen significant progress with targeted therapies.
  • Tyrosine kinase inhibitors (TKIs) are standard, but acquired resistance remains a major clinical challenge.
  • Recent trials (ADAURA, NeoADAURA, LAURA) established osimertinib across early and advanced NSCLC stages.

Purpose of the Study:

  • To review the evolving therapeutic landscape for EGFR-mutant NSCLC.
  • To discuss current challenges and future directions in managing treatment resistance.
  • To highlight advances in both early-stage and metastatic settings.

Main Methods:

  • Review of key clinical trials and emerging therapeutic strategies.
  • Analysis of combination therapies and resistance mechanisms.
  • Exploration of novel agents like bispecific antibodies and antibody-drug conjugates.

Main Results:

  • Osimertinib is the standard of care across NSCLC stages, but questions about adjuvant therapy duration and ctDNA-guided monitoring persist.
  • Frontline combinations (osimertinib + chemotherapy, amivantamab + lazertinib) improve outcomes in metastatic EGFR-mutant NSCLC.
  • Emerging strategies target resistance mechanisms like MET amplification and EGFR C797S, alongside novel drug classes.

Conclusions:

  • The treatment of EGFR-mutant NSCLC is becoming increasingly personalized and adaptive to resistance.
  • Optimal sequencing and combination strategies are crucial for maximizing patient benefit.
  • Future research focuses on overcoming resistance to achieve durable systemic and intracranial disease control.