Advances in Melanoma and Other Skin Cancers Research
NCI-funded researchers are working to advance our understanding of how to treat melanomaand other skin cancers. Much progress has been made in treating people whose melanoma has spread throughout their bodies (metastaticmelanoma). Yet many people still don't benefit from the newest drugs, and others often relapse after initially successful treatment.
This page highlights some of the latest research in treatment for melanoma and other skin cancers, including clinical advances that may soon translate into improved care, and research findings from recent studies.
Surgery remains the standard treatment for early-stage melanoma and may be used as part of therapy for more advanced disease. However, researchers are now focusing on developing treatments that directly target specific mutations in melanoma cells or that harness the body’s immune system to attack melanoma.
Targeted therapies use drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells. About half of people with melanoma that has metastasized, or that can’t be removed with surgery (unresectable melanoma), have mutations in the BRAF gene that produces the protein B-Raf. These mutations can lead to the growth of melanoma cells.
Researchers are studying how melanoma cells manage to grow in the presence of these targeted therapies, with the goal of finding ways to overcome resistance. Ideas being tested include new drug combinations and drugs that target the B-Raf pathway in different ways than existing drugs.
Immune Checkpoint Inhibitors
Immunotherapies are treatments that help the body’s immune system fight cancer more effectively. Melanoma tends to have a relatively high number of genetic mutations that can be recognized by the immune system compared with other cancer types. This makes it more likely that patients will respond to immunotherapies.
One type of immunotherapy, called immune checkpoint inhibition, has shown impressive results in some people with advanced melanoma. Three immune checkpoint inhibitors (ICIs) are now approved for the treatment of melanoma that can’t be removed with surgery or that has metastasized:
Unfortunately, ICIs only work in a minority of people with metastatic or unresectable melanoma, although patients whose tumors do shrink or disappear often have responses that last for years. Researchers are now testing ways to increase the number of people with melanoma who benefit from this type of treatment, such as:
Combining ICIs with general immune stimulants. Immune stimulants produce a type of chemical alarm in the body that tells the immune system that a threat exists. In one recent small clinical trial that combined pembrolizumab with a specific type of general immune stimulant, tumors shrank in almost 80% of people who received the two treatments together. Larger trials of this and other combinations of immunotherapy drugs are underway.
Testing new and existing ICIs in combination with targeted therapies and other types of drugs.
Harnessing the Body’s Immune Cells
Another type of immunotherapy, called adoptive cell therapy (ACT), is also being tested to treat patients with metastatic melanoma. ACT involves identifying those immune cells from a patient that are best at recognizing their tumor, growing a lot of those cells in the lab, and giving them back to the patient.
About half of patients with metastatic melanoma in early clinical trials of ACT saw their tumors shrink, and a quarter remained in remission for as long as the study tracked them—in some cases for up to a decade. But the procedure is complicated and expensive, and half of people do not benefit from the treatment at all or experience dangerous or even fatal side effects.
Researchers are looking for ways to make ACT work for more patients:
One idea being tested is to engineer immune cells collected from patients to be better at killing cancer cells before giving them back.
Another is to find common proteins in cancer cells that are recognized by immune cells.
Immunotherapy with Surgery for Advanced Melanoma
Adjuvant therapy is additional cancer treatment given after the primary treatment. Nivolumab, ipilimumab, and pembrolizumab have also been approved as adjuvant therapies for melanoma that has spread to nearby lymph nodes but can be removed with surgery. In recent clinical trials, all three immune checkpoint inhibitors reduced the risk of recurrence for some patients when given after surgery, although serious side effects were seen in many trial participants.
A follow-up clinical trial is now looking at whether some patients with earlier stage melanoma at high risk of recurrence may benefit from ICI therapy after surgery.
Melanoma researchers are also looking to understand how best to use existing therapies. One pressing question has been whether it is better for people who have melanoma with mutations in the gene that produces B-Raf to receive targeted drugs or ICIs as first-line therapy.
An ongoing NCI-sponsored trial is trying to answer this question. Participants are being randomly assigned to receive either a combination of targeted drugs or a combination of ICIs. When or if their cancer recurs, they will receive the other combination.
Researchers are also searching for biomarkers in melanoma that can predict which tumors might respond to available immunotherapies.
Rare Melanoma Types and Merkel Cell Carcinoma
Some rare types of melanoma have lagged behind in terms of advances in treatment. These include uveal melanoma, which starts in the eye; desmoplastic melanoma, a rare form of melanoma of the skin; and mucosal melanoma, which begins in the mucosal membranes, such as the linings of the nose and mouth.
However, recent small clinical trials suggest that these types of melanoma may also respond to immunotherapies. One NCI-sponsored trial is currently testing pembrolizumabin people with desmoplastic melanoma that can or cannot be removed with surgery.
In addition, more than half of patients with MCC in a small clinical trial had their tumors shrink or disappear during treatment with the ICI pembrolizumab, which received FDA approval for the treatment of MCC in 2018. Additional trials testing immunotherapies in this rare disease are underway.
Treatment for Advanced Basal Cell Carcinoma and Squamous Cell Carcinoma
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are the most common cancers in the United States. They rarely spread to other organs and are seldom fatal. But because they are so common, a substantial number of people are diagnosed with advanced BCC or SCC every year.
Recent breakthroughs in targeted therapies and immunotherapies have changed the way people with advanced BCC and SCC are treated. Ongoing research seeks to build on these breakthroughs such as:
The targeted drugs sonidegib (Odomzo) and vismodegib (Erivedge) can control tumors for a long time in some patients. However, resistance usually develops. In addition, side effects can cause some patients who need to take the drugs for a long time to stop taking them. Researchers are now looking for ways to change when and how much of these drugs are given, both to delay the development of resistance and to make them easier to tolerate. Immunotherapies are also being tested in people with advanced BCC.
In 2018, the FDA approved the first immunotherapy for metastatic SCC, an ICI called cemiplimab-rwlc (Libtayo) The success of this drug in advanced SCC showed that the immune system can be encouraged to recognize SCC cells. Based on this knowledge, people with metastatic SCC are now becoming eligible for new clinical trials of immunotherapy drugs and combinations.
For people whose BCC or SCC has not spread, surgery remains the mainstay of treatment. But less-intensive versions of radiation therapy have been developed for people who can’t tolerate surgery for larger tumors, such as the frail elderly.
Many NCI-funded researchers at the NIH campus, and across the United States and world, are seeking ways to address melanoma and other skin cancers more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts for melanoma and other skin cancers.
Scientists in the Division of Cancer Epidemiology and Genetics (DCEG) study families in which multiple members have developed certain cancers. In collaboration with the Melanoma Genetics Consortium (GenoMEL), DCEG researchers are searching for new genes in both melanoma-prone families and through a genome-wide association study to find genes that may increase the risk of melanoma.
NCI funds and oversees both early- and late-stage clinical trials to develop new treatments and improve patient care. Trials are available for melanoma prevention and treatmentand non-melanoma skin cancer prevention and treatment.
Melanoma and Other Skin Cancers Research Results
The following are some of our latest news articles about research on melanoma and other skin cancers:
ver historia personal en: www.cerasale.com.ar [dado de baja por la Cancillería Argentina por temas políticos, propio de la censura que rige en nuestro medio]//
weblog.maimonides.edu/farmacia/archives/UM_Informe_Autoevaluacion_FyB.pdf - //
weblog.maimonides.edu/farmacia/archives/0216_Admin_FarmEcon.pdf - //
www.proz.com/kudoz/english_to_spanish/art_literary/523942-key_factors.html - 65k - // www.llave.connmed.com.ar/portalnoticias_vernoticia.php?codigonoticia=17715 // www.frusculleda.com.ar/homepage/espanol/activities_teaching.htm // http://www.on24.com.ar/nota.aspx?idNot=36331 ||