Update on Melanoma – Doctors, Innovations, Trials in 2025 in Israel

Melanoma Treatment Update 2025: Latest Innovations, Doctors, and Breakthrough Therapies

Despite the fact that melanoma is one of the most aggressive types of skin cancer, in Israel there has seen remarkable advancements in treatment over the past few years.

In 2025, leading Israeli and global medical institutions continue to push the boundaries of immunotherapy, targeted therapy, and precision medicine, offering new hope for patients worldwide.

Top Melanoma Specialists in Israel in 2025

Leading Experts and Research Centers in Melanoma Treatment

We collaborate with such known professionals in melanoma field as:

Prof. Jacob Schachter – Chairman of the Ella Lemelbaum Institute for Immuno-Oncology, pioneering advanced TIL therapy and checkpoint inhibitors

Dr. Ronie Shapira – Head of the Ella Lemelbaum Institute, specializing in personalized immunotherapy and clinical trials

Prof. Jacob Peer – Eye Oncology Surgeon, Eye Department, Hadassah Jerusalem 

Whether you’re seeking a diagnosis, treatment plan, or a a Second Opinion of the leading Israeli melanoma specialist, these top doctors offer world-class care tailored to your needs.

These experts collaborate with international research teams to develop next-generation melanoma treatments, ensuring patients receive world-class care.

📞 Contact us today to explore your melanoma treatment options with leading Israeli doctors

Choose your doctor:

⇒ 8 Best Doctors for Melanoma in Israel in 2025

Breakthrough Treatments and New Medications for Melanoma 2025

1. Next-Generation Immunotherapy

Immunotherapy remains at the forefront of melanoma treatment, with immune-based therapies taking center stage.

In 2025, researchers have introduced next-generation checkpoint inhibitors, such as anti-LAG-3 antibodies, which enhance the body’s ability to fight melanoma cells when combined with existing PD-1 inhibitors like Keytruda and Opdivo.

One of the most promising therapies includes bispecific antibodies, which simultaneously target two immune checkpoints to boost the immune response against melanoma. Clinical trials have shown that these therapies improve survival rates while minimizing side effects.

A previous generation of immunotherapy for melanoma included the drug Ipilimumab (Yervoy), which blocks the protein CTLA-4. Blocking this protein can lead to a more powerful response from them against cancer cells.

Today, melanoma patients can be given a combination of PD-1 and CTLA-4 blockers to increase the therapeutic effect.

⇒ More details about Immunotherapy for Melanoma Treatment in 2025 

2. Tumor-Infiltrating Lymphocyte (TIL) Therapy Advances

Specialists of Israel at Sheba Medical Center and the Ella Lemelbaum Institute for Immuno-Oncology continue to refine TIL Therapy (Tumor Infiltrating Lymphocytes Therapy), an innovative approach for advanced metastatic melanoma patients, where immune cells are extracted from a patient’s tumor, multiplied in a lab, and reinfused to attack cancer. In 2025, enhanced TIL therapy, combined with new genetic modifications, is achieving higher success rates, particularly in advanced-stage melanoma patients who previously failed with other treatment options.

The goal of the treatment is to strengthen the patient’s own immune response against the malignant cells. The treatment is based on a technology that combines the transplantation of autologous lymphocyte cells that have activity against the patient’s melanoma cells together with chemotherapy and interleukin-2. 

The response rate of the treatment is currently about 40%, with partial to complete regression of the disease. The experimental treatment is provided in a limited number of centers around the world, including Sheba Medical Center.

⇒ More information about TIL Therapy for Melanoma in Israel

⇒ Patient’s Story After TIL

3. Personalized Targeted Therapies

Advancements in genomic profiling have led to new targeted drugs tailored to patients with specific genetic mutations such as BRAF, NRAS, and c-KIT mutations. The latest BRAF/MEK inhibitor combinations offer greater efficacy and reduced resistance compared to earlier treatments.

Additionally, Israeli biotech companies have developed novel small-molecule inhibitors that target secondary resistance mechanisms, making targeted therapy even more effective for long-term treatment.

About 50% of melanoma patients have a mutation in the BRAF gene. Biological drugs are aimed at inhibiting a specific mechanism in cancer cells, and may be very effective and cause the disease to regress. They try to prevent signal transmission pathways to tumor cells or to cells in its environment (such as blood vessels that feed it), usually by binding to a specific receptor. 

The MEK gene is closely related to the BRAF gene, so drugs that target MEK can also help treat melanoma with BRAF mutations. It has also been found that combining a BRAF inhibitor with a MEK inhibitor is more effective in treating melanoma than either type alone.

Biological drugs of the BRAF inhibitor for melanoma, such as Vemurafenib (Zelboraf®)*, Dabrafenib (Tafinlar®)*, Trametinib (Mekinist®)* Cobimetinib (Cotellic®)*, Encorafenib (Braftovi®)*, Binimetinib (Mektovi®)* work against the mutation, eliminating the protein’s overactivity and thus stopping the progression of the tumor. 

About 20% of patients will respond well to biological therapy even five years after it begins and their melanoma will quickly regress. However, many patients will develop resistance to this treatment after about a year or a year and a half, and then the next treatment will usually be immunotherapy.

These drugs are given in tablets and patients easily take them at home. 

⇒ More information about Targeted Therapy for Melanoma in Israel

4. mRNA-Based Cancer Vaccines

Following the success of mRNA technology in COVID-19 vaccines, researchers have developed mRNA-based melanoma vaccines, which train the immune system to recognize and destroy cancer cells. Clinical trials conducted in Tel Aviv Sourasky Medical Center indicate that these vaccines, when combined with checkpoint inhibitors, significantly reduce the risk of melanoma recurrence.

This treatment is on the study stage and is not yet approved.

5. Surgery

Most people diagnosed with melanoma will be operated on after a biopsy has confirmed the diagnosis, with a wide local excision. In cases where multiple foci of metastases are found, surgery will not be indicated.

Wide local excision
In a wide excision, which is performed with a sentinel node biopsy, the surgeon removes a small portion of the tissues that appear normal in the area surrounding the tumor (margins).

This operation is required to ensure that no cancer cells remain, and reduces the risk of the disease recurring.

If the thickness of the cancerous tumor is less than 1 mm, it will be necessary to remove one centimeter of healthy skin (if the surgery does not require a sentinel node biopsy – it can be performed under local anesthesia).

If the melanoma is thicker than 1 mm, the incision will be extended to include 2 cm of healthy skin on each side of the initial biopsy scar.

Skin graft
When a large area of ​​skin is removed during surgery, the surgeon will remove a layer of skin from another area of ​​the body (usually the thigh), and place it over the surgical wound. 

Complete sentinel lymph node dissection – SLND
If tests show that the lymph nodes are infected (or after an ultrasound-guided biopsy or a sentinel node is found to be infected), another operation will be performed to remove them. The operation will be performed under general anesthesia and will require a 1-3 day hospital stay.

Eye melanoma – Tumor resection

In cases where the melanoma is limited in size, especially when it is located in the front part of the eye, the tumor can be resected after creating a “window” in the wall of the eye. The surgeries are only suitable for tumors with a small diameter. 

6. Radiotherapy

Radiation can also be given to patients with advanced melanoma to locally control metastases or to improve the response to immunotherapy. In addition, radiation can be a supportive (palliative) treatment – ​​relieving symptoms such as pain and bleeding caused by the tumor or its metastases – which improves quality of life.

Radiotherapy uses high-energy rays to destroy cancer cells. Radiation is sometimes given to the area where lymph nodes were removed during surgery, especially if they contained a lot of cancer cells, to reduce the chance of the disease coming back.

Radiation is also used to treat melanoma that has come back after surgery, either in the skin or lymph nodes, or to treat distant spread of the disease.

It is most often given in the following cases:

• Radiation given to the skin or lymph nodes distant from the original melanoma – radiation is sometimes used to shrink the size of the lymph nodes and relief pain.
• To the bones – radiation can help reduce bone pain and swelling.
• To the brain – radiation can help shrink a secondary brain tumor and improve symptoms. A newer technique is a single, highly focused radiation treatment to the head, called stereotactic radiosurgery (SRS).
• Brachytherapy (local radiation) – The most common treatment method for iris melanomas (uveal melanoma).

7. Chemotherapy

It is not currently accepted to give systemic (whole-body) chemotherapy as a first-line treatment for advanced melanoma. However, there are cases where chemotherapy will be used as an advanced line of treatment, after exhausting previous lines.

Two chemotherapy drugs are used:

• Dacarbazine (DTIC)*
• Temozolomide (Temodal®)*

Isolated limb perfusion (ILP)

In the case of local recurrence of melanoma in the same limb where the original melanoma developed and if surgery is not appropriate, the doctor may suggest a special procedure that allows high-dose chemotherapy to be given directly to just one limb (leg or arm). The treatment is given while a tight band is wrapped around the isolated area, preventing the chemotherapy from passing to other parts of the body. This greatly reduces the common side effects of chemotherapy.

This is a one-time treatment that is performed only in some hospitals in Israel, under general anesthesia, and involves a hospital stay of about a week to 10 days. At the end of the procedure, the limb will need to be monitored and elevated.

Lymphedema – swelling of the lymph nodes in a limb – may occur, which can develop long after treatment.

Israeli healthcare team will explain you about side effects before the treatment. 

Ongoing Clinical Trials and Future Prospects

Clinical trials play a vital role in bringing innovative treatments to patients. In 2025, several high-impact trials are underway in Israel and globally:

• Combination Therapy Trials: New strategies combining TIL therapy, immune checkpoint inhibitors, and oncolytic viruses show promising remission rates.
• Neo-Adjuvant Therapy Trials: Testing pre-surgical immunotherapy to shrink tumors before removal, improving long-term survival.
• AI-Driven Drug Discovery Trials: AI-powered platforms are being used to identify new drug candidates, accelerating the development of highly effective melanoma treatments.

It is important to remember that every treatment is thoroughly studied in preliminary studies before being tested in randomized, controlled clinical trials.

To ensure patient safety and their rights, each experimental protocol receives approval from an ethics committee, called the Helsinki Committee, on behalf of the medical institution where the study will be conducted.

If you match the study requirements, you will receives a copy of the protocol and accompanying documents. It is required to read it and sign an informed consent form before the study begins. Signing the form means that the participant knows what the study is about, understands why it is being conducted, why they were invited to participate in it, and how they will be involved in it.

Even after you have agreed to participate in the study, you can withdraw from it at any time. The decision not to participate in the trial or to withdraw from it will not affect the doctor’s attitude in any way, and he will continue to provide the best accepted treatment.

List of Skin Cancer and Malignant Melanoma Clinical Trials in Israel – 2025

• Effect of Crizanlizumab Alone or in Combination with Nivolumab in Patients with Glioblastoma and Melanoma with Brain Metastases (NCT05909618)
• Treatment with Investigational Drugs with or without Pembrolizumab (Keytruda) or Pembrolizumab Alone in Melanoma Patients with Brain Metastases: Substudy 02D (Study MK-3475-02D / KN U02 – 02D)
• Study for Patients with Non-Dissecting and/or Metastatic Melanoma to Filter Soluble Colloids from Blood Plasma, with or without Nivolumab
• Treatment with Investigational Drugs – MK-7684/V937 – with/without Pembrolizumab (Keytruda) or Pembrolizumab Alone for Melanoma (Study MK-3475-02C)
• BMC12 in combination with nivolumab in melanoma patients
• A study to evaluate the safety and efficacy of fecal transplantation in combination with nivolumab in MSI-high/dMMR patients who have failed immunotherapy (NCT04521075)
• Investigational drug treatment with/without pembrolizumab (Keytruda) or pembrolizumab alone in melanoma (Study MK-3475-02A / 2019-003956-35)
• Nivolumab with ralutlimab administered subcutaneously versus intravenously in participants with previously untreated or unresectable metastatic melanoma (NCT05625399)
• IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated melanoma who have not Surgically resectable, or metastatic (NCT05155254)
• Phase I dose escalation study of the preliminary antitumor activity of RO7247669, a PD1-LAG3 antibody, in patients with advanced and/or metastatic melanoma (NP41300)
• Encorfenib and binimatinib in combination with pembrolizumab versus placebo in combination with pembrolizumab in participants with locally advanced, metastatic, or unresectable melanoma positive for the BRAF V600E/K mutation Identification: NCT04657991
• Profiling the response to anticancer therapy in oncology patients receiving immunotherapy and/or chemotherapy to establish a profile to predict response to these therapies (Melanoma – PROPHETIC study / OH-HRPP-001)
• CM24 in combination with nivolumab in melanoma patients
• Alpha Radiation in Malignant Tumors of the Skin and Mucosal Tissues (Skin Cancer) (DaRT/ CTP-CMN-02_ / CTP-CMN-02 Study)
• Pembrolizumab (Keytruda)/Placebo as Adjuvant Therapy after Surgery and Radiation for High-Risk Locally Advanced Squamous Cell Carcinoma (LA cSCC Study / KEYNOTE-630)
• Treatment with Investigational Drugs with or without Pembrolizumab (Keytruda) or Pembrolizumab Alone in Melanoma Patients: Substudy 02B (Study MK-3475-02B / KN U02 – 02B)

Source: Israeli Cancer Association – cancer.org.il

A New Era of Melanoma Treatment in Israel

With groundbreaking immunotherapy, targeted drugs, genetic profiling, and mRNA vaccines, 2025 marks a new era in melanoma treatment. Israeli doctors and global researchers continue to innovate, providing patients with better survival rates and improved quality of life.

If you or a loved one are seeking expert consultations, second opinions, or access to cutting-edge melanoma treatments, our team is here to guide you through the latest options available in Israel.

Melanoma Diagnosis in Israel