Related Experiment Video

Updated: Apr 18, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

668

Cutaneous adverse effects of targeted therapies: Part II: Inhibitors of intracellular molecular signaling pathways

James B Macdonald1, Brooke Macdonald2, Loren E Golitz3

  • 1Department of Dermatology, Central Utah Clinic, Provo, Utah; Department of Pathology, Central Utah Clinic, Provo, Utah.

Journal of the American Academy of Dermatology
|January 17, 2015
PubMed

Insights

Targeted cancer therapies, including those for melanoma and basal cell carcinoma, frequently cause skin side effects. Dermatologists play a key role in managing these toxicities from targeted agents and immunotherapies.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Targeted therapies have revolutionized cancer treatment, particularly for metastatic melanoma and basal cell carcinoma.
  • Deregulation of intracellular signaling pathways like PI3K-AKT-mTOR and RAS-RAF-MEK-ERK is implicated in various cancers.
  • Cutaneous adverse effects are common toxicities associated with targeted cancer treatments and immunotherapies.

Purpose of the Study:

  • To review the skin-related adverse sequelae of targeted oncotherapies.
  • To discuss the frequency and implications of cutaneous toxicities from specific targeted agent classes.
  • To highlight the essential role of dermatologists in supportive care for cancer patients undergoing targeted treatments.

Main Methods:

  • Review of literature on targeted therapies in dermatology and their associated cutaneous toxicities.
  • Analysis of adverse events linked to inhibitors of RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, hedgehog signaling pathways, and immunotherapies.
  • Focus on on- and off-target effects of these targeted agents.

Main Results:

  • Targeted therapies for skin cancers and other malignancies frequently induce dermatologic adverse events.
  • Inhibitors of RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, hedgehog signaling, and immunotherapies are associated with a range of skin toxicities.
  • Understanding the frequency and implications of these toxicities is crucial for patient management.

Conclusions:

  • Dermatologists are integral to managing the frequent skin toxicities arising from novel oncotherapies.
  • Supportive dermatologic care is essential for patients receiving targeted agents and immunotherapies.
  • This review provides insights into managing on- and off-target cutaneous toxicities.
Keywords:
AKT inhibitorB-RAFMAP kinase pathwayMEK inhibitorsPD-1 inhibitorPI3 kinase inhibitorPI3K-AKT-mTOR pathwayRAF inhibitorsRASautoimmune adverse effectsautoimmune dermopathiesdabrafenibdermatitisdual inhibitordysgeusiaeverolimushair losshedgehog signaling pathwayimmune-related toxicitiesimmunotherapyipilimumabkeratoacanthomakeratosis pilariskeratotic squamoproliferative lesionlambrolizumabloss of tastemTOR inhibitornivolumabpanniculitispruritusrapamycinseborrheic dermatitisselumetinibsquamous cell carcinomataste alterationtemsirolimustrametinibvemurafenibverrucal keratosisvismodegibvitiligo

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.4K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.7K

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...
9.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

1.8K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.3K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.6K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
8.5K