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Related Concept Videos

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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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.
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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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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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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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Metastasis02:30

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Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
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Related Experiment Video

Updated: Jun 1, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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HER2-Positive Breast Cancer Treatment and Resistance.

Jamunarani Veeraraghavan1,2,3, Carmine De Angelis1,2, Carolina Gutierrez1,2

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Advances in Experimental Medicine and Biology
|January 17, 2025
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HER2-positive breast cancer treatments improved outcomes, but resistance remains a challenge. Understanding resistance mechanisms is crucial for developing new therapies to overcome treatment failure.

Keywords:
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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • HER2-positive breast cancer is aggressive, historically with poor prognosis.
  • Trastuzumab and subsequent HER2-targeted therapies significantly improved patient outcomes.
  • Treatment resistance is a major clinical challenge in HER2-positive breast cancer management.

Purpose of the Study:

  • To review the mechanisms underlying resistance to HER2-targeted therapies.
  • To highlight the importance of understanding resistance for developing novel treatment strategies.
  • To discuss emerging targeted agents and approaches to overcome resistance.

Main Methods:

  • Review of scientific literature on HER2-targeted therapies and resistance mechanisms.
  • Analysis of molecular pathways involved in treatment resistance.
  • Synthesis of information on current and future therapeutic strategies.

Main Results:

  • Resistance mechanisms include HER receptor reactivation and downstream signaling pathway deregulation (e.g., PI3K/AKT, RAS/MEK/ERK).
  • Compensatory pathways (e.g., ER, other RTKs, metabolic pathways) can also drive resistance.
  • Tumor microenvironment alterations contribute to treatment resistance.
  • New targeted agents and approaches are under investigation to overcome resistance.

Conclusions:

  • Understanding the mechanistic underpinnings of resistance is essential for effective treatment development.
  • Targeting key drivers of resistance, including tumor epithelial cell-specific and microenvironment-related mechanisms, is a promising strategy.
  • Ongoing research is identifying new therapeutic vulnerabilities and agents to combat anti-HER2 treatment resistance.