Related Experiment Video
Updated: Sep 27, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Human melanoma: drug resistance
Heike Helmbach1, Pranav Sinha, Dirk Schadendorf
1Klinische Kooperationseinheit für Dermatoonkologie (DKFZ) an der Universitäts-Hautklinik Mannheim, Universität Heidelberg, 68135 Mannheim, Germany.
Abstract:
Advanced malignant melanoma has a poor prognosis since chemotherapy is mostly ineffective because, in part, of the intrinsic and/or extrinsic resistance of melanoma cells to systemic treatment with antineoplastic agents. The reasons for the chemoresistant phenotype are currently unknown. The relevance of well-analyzed drug resistance mechanisms in melanoma such as intracellular and extracellular transport, drug resistance by induction of certain enzyme systems, and altered drug-target interaction is reviewed. It has been shown that most anticancer drugs kill susceptible cells through induction of apoptosis. Therefore, the significance of apoptotic deficiency caused by alteration in the apoptotic pathway is discussed in relation to specific molecules and apoptotic mechanisms like death-receptors, the Bcl-2 family, and the Hsp family of proteins. The complexity of the molecular variants involved in signal transduction along apoptotic pathways suggests that the cell may possess a variety of possibilities for regulating apoptosis and generating apoptosis deficiency. Thus apoptosis and apoptosis deficiency should be analyzed to understand the mechanisms of melanoma resistance.
Insights
Melanoma cells resist chemotherapy due to unknown mechanisms. Understanding apoptosis deficiency is key to overcoming this resistance in advanced malignant melanoma.
Area of Science:
- Oncology
- Cancer Biology
- Dermatology
Background:
- Advanced malignant melanoma presents a poor prognosis due to chemotherapy ineffectiveness.
- Melanoma cell resistance to antineoplastic agents is a significant clinical challenge.
- The precise reasons for the chemoresistant phenotype in melanoma remain largely unknown.
Purpose of the Study:
- To review known drug resistance mechanisms in melanoma.
- To discuss the role of apoptosis and apoptotic deficiency in chemoresistance.
- To highlight the complexity of apoptotic pathways and their regulation.
Main Methods:
- Literature review of established drug resistance mechanisms.
- Analysis of apoptosis induction by anticancer drugs.
- Discussion of molecular alterations in apoptotic pathways (e.g., Bcl-2 family, Hsp family).
Main Results:
- Chemotherapy resistance in melanoma involves mechanisms like altered drug transport and enzyme activity.
- Most anticancer drugs induce apoptosis in susceptible cells.
- Deficiency in apoptosis, caused by alterations in apoptotic pathways, contributes significantly to chemoresistance.
Conclusions:
- Apoptosis deficiency is a critical factor in melanoma's chemoresistance.
- Understanding the molecular regulation of apoptosis is essential for developing effective melanoma treatments.
- Targeting apoptotic pathways may offer novel therapeutic strategies for advanced melanoma.
Related Concept Videos
02:56Treatment Resistant Cancers
02:56Treatment Resistent Cancers
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:50Combination Therapies and Personalized Medicine
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...