Decoding Melanoma Development and Progression: Identification of Therapeutic Vulnerabilities

Melanoma, a cancer of the skin, arises from transformed melanocytes. Melanoma has the highest mutational burden of any cancer partially attributed to UV induced DNA damage. Localized melanoma is “curable” by surgical resection and is followed by radiation therapy to eliminate any remaining cancer cells. Targeted therapies against components of the MAPK signaling cascade and immunotherapies which block immune checkpoints have shown remarkable clinical responses, however with the onset of resistance in most patients, and, disease relapse, these patients eventually become refractory to treatments. Although great advances have been made in our understanding of the metastatic process in cancers including melanoma, therapy failure suggests that much remains to be learned and understood about the multi-step process of tumor metastasis. In this review we provide an overview of melanocytic transformation into malignant melanoma and key molecular events that occur during this evolution. A better understanding of the complex processes entailing cancer cell dissemination will improve the mechanistic driven design of therapies that target specific steps involved in cancer metastasis to improve clinical response rates and overall survival in all cancer patients.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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CONCLUSION In this large study evaluating efficacy of adjuvant RT in DM, no overall survival benefit was observed among patients receiving adjuvant RT.
Source: Dermatologic Surgery - Category: Dermatology Tags: Original Article Source Type: research
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211039952. doi: 10.1177/15330338211039952.ABSTRACTCholangiocarcinoma is a general term for intrahepatic and extrahepatic malignant tumors deriving in the biliary system. According to the location, it is divided into intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma. Progressive cholangiocarcinoma yields poor outcomes with radiotherapy; therefore, there is an urgent need for new therapeutic breakthroughs. Immune checkpoint inhibitor (ICI) therapy brings the treatment for cancer into a new field, with the use of drugs targeting PD-1/PD-L...
Source: Technology in Cancer Research and Treatment - Category: Cancer & Oncology Authors: Source Type: research
Clin Cancer Res. 2021 Jul 20:clincanres.1193.2021. doi: 10.1158/1078-0432.CCR-21-1193. Online ahead of print.ABSTRACTThe impact of liver metastases on immune checkpoint inhibitor effectiveness in patients with solid tumor malignancies has been the focus of several recent clinical and translational studies. We review the literature describing the immune functions of the liver and particularly the mechanistic observations in these studies. The initial clinical observation was that pembrolizumab appeared to be much less effective in melanoma and NSCLC patients with liver metastasis. Subsequently other clinical studies have ex...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Source Type: research
CONCLUSIONS: This analysis suggests that treatment with SRS and immunotherapy is associated with improved OS compared to immunotherapy alone for patients with melanoma or NSCLC metastatic to the brain.PMID:34236616 | DOI:10.1007/s12094-021-02675-w
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Malignant melanoma is the 5th most common cancer and stage IV melanoma accounts for approximately 4% of new melanoma diagnoses in the United States. The prognosis for regionally advanced disease is poor, but there have been numerous recent advances in the medical management of melanoma in-transit metastases. The goal of this paper is to review currently accepted treatment options for in-transit metastases and introduce emerging therapies. Therapies to be discussed include limb perfusion and infusion, immunotherapy, checkpoint inhibitors, and radiation therapy.
Source: Clinics in Plastic Surgery - Category: Cosmetic Surgery Authors: Source Type: research
AbstractRadiotherapy for brain metastases has evolved tremendously over the past four decades, allowing for improved intracranial control of disease with reduced neurotoxicity. The main technological advance was provided by volumetric modulated arc therapy (VMAT), a computer-controlled delivery method that has opened the door for single-isocenter multi-metastases stereotactic radiosurgery (SRS) and hippocampal avoidance whole brain radiation therapy (HA-WBRT). Other notable advances have occurred in the combination of immune checkpoint inhibitors (ICI) and radiosurgery. When these two modalities are combined in the proper ...
Source: Clinical and Experimental Metastasis - Category: Cancer & Oncology Source Type: research
This article will review background data establishing efficacy of angiogenesis inhibitors and immunotherapy in the treatment of cervical cancer as well as results of prospective studies combining targeted therapies with standard CRT with the aim of improving outcomes. In addition, the role of immunotherapy and radiation on the tumor microenvironment (TME) will be discussed.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Neelu Puri Malignant melanoma is the most aggressive type of skin cancer with invasive growth patterns. In 2021, 106,110 patients are projected to be diagnosed with melanoma, out of which 7180 are expected to die. Traditional methods like surgery, radiation therapy, and chemotherapy are not effective in the treatment of metastatic and advanced melanoma. Recent approaches to treat melanoma have focused on biomarkers that play significant roles in cell growth, proliferation, migration, and survival. Several FDA-approved molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) have been developed against ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
We examined the real ‐world survival impact of IT and RT combination and timing strategies.Materials and MethodsFrom the facility ‐based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28–90 days of RT. The co‐primary outcomes were propensity score‐adjusted overall survi...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
CONCLUSION Vulvar malignancies are rare, and diagnosis is dependent on biopsy and pathologic evaluation. Treatment for vulvar malignancies depends on histopathologic diagnosis but ranges from wide local excision with or without lymph node biopsy or dissection to radiation therapy with chemo- or immunotherapy. Overall survival varies by diagnosis.
Source: Dermatologic Surgery - Category: Dermatology Tags: Review Article Source Type: research
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