Related Experiment Video
Updated: Oct 31, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Therapeutic Advancements Across Clinical Stages in Melanoma, With a Focus on Targeted Immunotherapy
Claudia Trojaniello1, Jason J Luke2, Paolo A Ascierto1
1Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy.
Abstract:
Melanoma is the most fatal skin cancer. In the early stages, it can be safely treated with surgery alone. However, since 2011, there has been an important revolution in the treatment of melanoma with new effective treatments. Targeted therapy and immunotherapy with checkpoint inhibitors have changed the history of this disease. To date, more than half of advanced melanoma patients are alive at 5 years; despite this breakthrough, approximately half of the patients still do not respond to treatment. For these reasons, new therapeutic strategies are required to expand the number of patients who can benefit from immunotherapy or combination with targeted therapy. Current research aims at preventing primary and acquired resistance, which are both responsible for treatment failure in about 50% of patients. This could increase the effectiveness of available drugs and allow for the evaluation of new combinations and new targets. The main pathways and molecules under study are the IDO inhibitor, TLR9 agonist, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2 (NKTR-214), GITR, and adenosine pathway inhibitors, among others (there are currently about 3000 trials that are evaluating immunotherapeutic combinations in different tumors). Other promising strategies are cancer vaccines and oncolytic viruses. Another approach is to isolate and remove immune cells (DCs, T cells, and NK cells) from the patient's blood or tumor infiltrates, add specific gene fragments, expand them in culture with growth factors, and re-inoculate into the same patient. TILs, TCR gene transfer, and CAR-T therapy follow this approach. In this article, we give an overview over the current status of melanoma therapies, the clinical rationale for choosing treatments, and the new immunotherapy approaches.
Insights
Advanced melanoma treatment has improved significantly with targeted therapy and immunotherapy, yet resistance remains a challenge. Ongoing research focuses on overcoming resistance and exploring novel immunotherapies to improve patient outcomes.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Melanoma is a deadly skin cancer, with early stages treatable by surgery.
- Since 2011, targeted therapy and immunotherapy have revolutionized advanced melanoma treatment, improving 5-year survival rates.
- Despite advances, approximately 50% of advanced melanoma patients do not respond to current treatments, necessitating new strategies.
Purpose of the Study:
- To provide an overview of current melanoma therapies and their clinical rationale.
- To explore novel immunotherapy approaches for melanoma treatment.
- To discuss strategies for preventing primary and acquired resistance to melanoma therapies.
Main Methods:
- Review of current literature on melanoma treatment advancements.
- Analysis of emerging immunotherapy targets and strategies, including checkpoint inhibitors, IDO inhibitors, TLR9 agonists, STING, LAG-3, TIM-3, HDAC inhibitors, pegylated IL-2, GITR, and adenosine pathway inhibitors.
- Discussion of novel approaches such as cancer vaccines, oncolytic viruses, and adoptive cell therapies (TILs, TCR gene transfer, CAR-T).
Main Results:
- Significant progress in advanced melanoma treatment due to targeted therapy and immunotherapy.
- Identification of resistance mechanisms as a key factor in treatment failure for about 50% of patients.
- Emergence of numerous new therapeutic targets and strategies currently under investigation in clinical trials.
Conclusions:
- While immunotherapy and targeted therapy have transformed melanoma treatment, overcoming resistance is crucial.
- Further research into novel immunotherapies, combination treatments, and resistance-preventing strategies is essential to improve outcomes for all melanoma patients.
- Adoptive cell therapies and other innovative approaches hold promise for future melanoma treatment paradigms.
More Related Videos
Related Concept Videos
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
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...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
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...