Of all the skin cancer types, melanoma, the cancer of pigmented melanocytes is the most aggressive. Despite the development of revolutionary targeted inhibitors (BRAF and MEK inhibitors) and immune check point inhibitors, melanoma patients have surprisingly poor prognosis. This is mostly attributed to the development of intrinsic or acquired resistance against therapeutic approaches. The resistance is driven by mutational and non-mutational events and by dysregulation of the melanoma microenvironment. Common mechanisms, which are not yet described completely, include bypassing the dependency of melanoma cells on the mitogen activated pathway kinases (MAPKs), and evasion of the anti-melanoma immune response. In addition, non-genetic mechanisms like lineage plasticity, extracellular matrix modulations, and “non-classical” signaling through melanin-chemiexcitation, has also been suggested to be possible resistance mechanism. Since the genetic and non-genetic events responsible for resistance, and the direct and indirect (through melanin-chemiexcitation) impacts of melanoma carcinogens like ultraviolet radiation (UV), are person specific, this suggests a requirement for personalized treatment regimens. For this to be successful, we first need to characterize the drug-target interactions, feedback loop signaling, immunogenicity and immune response, and the tumor microenvironment globally and specifically in a patient specific manner. The current Research Topic will focus on all such clinical, technical, and personalized issues.
We welcome original research articles, reviews and commentaries focusing on recent advances in the therapy resistance mechanisms with a particular focus on the following topics:
1. Targeted therapy resistance and feed back loop signaling, especially the delayed and paradoxical upregulation of the MAPK pathways.
2. Interactions between various MAPK pathways like ERK, p38, and JNK, and its impact on the therapy response.
3. Interaction between the targeted therapy and immunotherapy.
4. Pigmentation in melanoma and its impact on the therapeutic strategies.
Of all the skin cancer types, melanoma, the cancer of pigmented melanocytes is the most aggressive. Despite the development of revolutionary targeted inhibitors (BRAF and MEK inhibitors) and immune check point inhibitors, melanoma patients have surprisingly poor prognosis. This is mostly attributed to the development of intrinsic or acquired resistance against therapeutic approaches. The resistance is driven by mutational and non-mutational events and by dysregulation of the melanoma microenvironment. Common mechanisms, which are not yet described completely, include bypassing the dependency of melanoma cells on the mitogen activated pathway kinases (MAPKs), and evasion of the anti-melanoma immune response. In addition, non-genetic mechanisms like lineage plasticity, extracellular matrix modulations, and “non-classical” signaling through melanin-chemiexcitation, has also been suggested to be possible resistance mechanism. Since the genetic and non-genetic events responsible for resistance, and the direct and indirect (through melanin-chemiexcitation) impacts of melanoma carcinogens like ultraviolet radiation (UV), are person specific, this suggests a requirement for personalized treatment regimens. For this to be successful, we first need to characterize the drug-target interactions, feedback loop signaling, immunogenicity and immune response, and the tumor microenvironment globally and specifically in a patient specific manner. The current Research Topic will focus on all such clinical, technical, and personalized issues.
We welcome original research articles, reviews and commentaries focusing on recent advances in the therapy resistance mechanisms with a particular focus on the following topics:
1. Targeted therapy resistance and feed back loop signaling, especially the delayed and paradoxical upregulation of the MAPK pathways.
2. Interactions between various MAPK pathways like ERK, p38, and JNK, and its impact on the therapy response.
3. Interaction between the targeted therapy and immunotherapy.
4. Pigmentation in melanoma and its impact on the therapeutic strategies.