NRAS Melanoma | Primary Research (KOL's Insight) | Market Intelligence | Epidemiology & Market Forecast-2035

About one-third of all human cancers have RAS oncogene activating mutations. A fifth or so of cutaneous melanomas have NRAS mutations, which are associated with aggressive clinical behavior. It is currently known that mutations in NRAS, KRAS, and HRAS are present in 20%, 2%, and 1% of all melanomas, respectively. NRAS was the first melanoma oncogene to be discovered. There is currently no approved targeted therapy for NRAS-mutated melanoma, and immune-based therapies are used to treat metastatic patients first.

Description

Since NRAS was the first melanoma oncogene identified, it is now known that mutations in NRAS, KRAS, and HRAS account for 20%, 2%, and 1% of all melanomas, respectively. The majority (>80%) of NRAS variants result from a point mutation at position 61 that changes glutamine into leucine. These mutations prevent NRAS from becoming inactive (GTP-bound) due to upstream RTK activation. They also decrease GTPase activity. Even though early detection and surgical removal of cutaneous melanoma unquestionably increase patient survival rates, once the cancer has spread, successful treatment becomes more difficult and the outlook for most patients is grim. NRAS melanomas are more aggressive than BRAF or triple WT subtypes and have a lower median overall survival rate as a result. This poor prognosis is also a result of the slow development of targeted therapies: while the first BRAF inhibitors were approved by the FDA/EMA almost ten years ago, followed by the introduction of even more effective combination therapies targeting BRAF and MEK, therapeutic options for NRAS melanoma patients are still limited.

NRAS Melanoma (Epidemiology)

The distribution of oncogenic mutations in these tumors can be used to predict how melanoma, a diverse group of melanocytic neoplasms, will behave biologically. About one-third of all human cancers have been found to have mutations that activate the RAS oncogene. A fifth or so of all cutaneous melanomas have NRAS mutations, which are associated with aggressive clinical behavior. When several signaling cascades, including PI3K/Akt, MEK-ERK, and RAL, are activated in cells with oncogenic NRAS mutations, this encourages the spread of the cancer. The first oncogene discovered in melanoma, NRAS, is responsible for 20% of all melanomas. The majority of NRAS mutations (>80%) involve a point mutation that converts glutamine to leucine at position 61. Regardless of whether upstream RTKs are activated, these mutations impair GTPase activity and keep NRAS in its activated (GTP-bound) state.

NRAS Melanoma -Current Market Size & Forecast Trends

The market for NRAS-mutant melanoma is currently part of the broader melanoma treatment landscape, which was valued at approximately USD 3.9 billion in 2023 and is expected to reach around USD 8.9 billion by 2034, with a compound annual growth rate (CAGR) of about 7.93%. NRAS mutations are found in approximately 20% of melanoma cases and are associated with a more aggressive disease course and poorer outcomes compared to other types of melanoma. Despite the advancements in targeted therapies for BRAF mutations, effective treatment options for NRAS-mutant melanoma remain limited, necessitating ongoing research into new therapeutic strategies, including MEK inhibitors and combination therapies. As awareness and understanding of NRAS-driven melanoma improve, the market is expected to expand significantly through 2035, driven by innovations in treatment and increased investment in research targeting this specific mutation.

Since there is currently no approved targeted therapy for melanoma with an NRAS mutation, metastatic patients are treated with immune-based therapies first before switching to second-line cytotoxic chemotherapy with drugs like carboplatin/paclitaxel (C/P), dacarbazine (DTIC), or temozolomide (TMZ). The discovery of germline mutations or variants in genes that affect inflammatory response may also help us understand the basis of response to immune-targeted medications, as recently demonstrated with a patient with lung adenocarcinoma who had an exceptional response to anti-PD-L1 therapy and was found to have a germline JAK3 mutation. Additionally, tumors can be profiled for acquired mutations that affect how well they respond to treatments. Combinations of targeted agents with immune checkpoint inhibitors, as has been suggested for BRAF mutant melanoma, may be a viable option to increase both response rates and longevity of responses with a better understanding of NRAS melanoma and immunotherapy response determinants. To reduce toxicity and efficacy loss, however, careful agent selection and close monitoring will be required.

Report Highlights

NRAS Melanoma - Current Market Trends

NRAS Melanoma - Current & Forecasted Cases across the G8 Countries

NRAS Melanoma - Market Opportunities and Sales Potential for Agents

NRAS Melanoma - Patient-based Market Forecast to 2035

NRAS Melanoma - Untapped Business Opportunities

NRAS Melanoma - Product Positioning Vis-a-vis Competitors' Products

NRAS Melanoma - KOLs Insight