ABSTRACT
In some molecular targeted therapies, skin disorders including acne-like rashes or maculopapular rashes frequently appear, which are often clinically problematic. In Kampo medicine, it has been reported that the combination of jumihaidokuto and orengedokuto (hereinafter called JHT + OGT) is effective for acne. In this study, we report the experiences of JHT + OGT for the treatment of rashes caused by molecular targeted therapies. We extracted patients from June 2013 to June 2017 who took molecular targeted therapies and the treatment with JHT + OGT for skin rashes. The primary endpoint was severity of rashes before and after treatment by JHT + OGT (judged by CTCAE v4.0). In 22 patients (14 males and 8 females), the rashes after treatment with JHT + OGT significantly improved compared with those before treatment (from the median grade of 2 to 1 [p = 0.011]), with 14 cases of improvement, 6 cases of no change, and 2 cases of deterioration. It was suggested that JHT + OGT for skin rashes caused by molecular targeted therapies could be one of the treatment options.
ABSTRACT
Despite advances in cancer therapy, gastric cancer has a poor prognosis and high cancer-related mortality. Based on the molecular characteristics of cancer, specific targeted therapies have shown clinical benefits for various tumors. In addition, immunotherapy using immune checkpoint inhibitors has led to a paradigm shift in cancer treatment and shown remarkable results in some solid tumors. Although immunotherapy has been actively applied to gastric cancer, the efficacy is unsatisfactory compared with other solid tumors, such as melanoma and lung cancers. This is because of the complex mechanism of gastric cancer, tumor heterogeneity, heterogeneity among patients, and the absence of appropriate biomarkers to predict response. An effective new cancer treatment strategy that combines targeted therapies and various immunotherapies based on biological markers such as tumor mutation burden and microsatellite instability is urgently needed. Furthermore, customized treatment is necessary to overcome tumor heterogeneity.
Subject(s)
Humans , Biomarkers , Immunotherapy , Lung Neoplasms , Melanoma , Microsatellite Instability , Molecular Targeted Therapy , Mortality , Population Characteristics , Prognosis , Stomach NeoplasmsABSTRACT
Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.
Subject(s)
Biomarkers , Breast Neoplasms , Kidney Neoplasms , Leukemia, Lymphocytic, Chronic, B-Cell , Molecular Targeted Therapy , Neuroendocrine Tumors , Oncogene Protein v-akt , Signal Transduction , Stomach Neoplasms , TOR Serine-Threonine KinasesABSTRACT
Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.