The scope of nanoparticle therapies for future metastatic melanoma treatment

Abstract

Metastatic melanoma is a highly aggressive malignancy that has traditionally been very difficult to treat. However, after decades of basic research into the signal transduction pathways that promote cancer cell survival, chemoresistance, growth, and crosstalk with the immune system, targeted therapies have now been developed that offer improved survival for patients with metastatic melanoma. Some of the most promising therapies that have been developed include ipilimumab, an anti-cytotoxic T lymphocyte antigen 4 antibody that enhances T-cell activity in the tumour, and selective BRAF inhibitors, such as vemurafenib that blocks tumour cell proliferation in patients with activating BRAF mutations. Although these treatments offer substantial hope for patients, they are not without their drawbacks, which include adverse side-effects, drug resistance, and eventual relapse. Nanotherapeutics holds significant promise to circumvent these shortcomings and has the additional advantage of potentially functioning as a diagnostic device. We will discuss the scope of the use of such multimodal nanoparticles for melanoma treatment and ask whether such particles can offer patients with metastatic melanoma improved prognoses for the future.

Nanoparticle–Dendrimer Hybrid Nanocapsules for Therapeutic Delivery

“…We initially studied the biodistribution of NDHCs in mice organs, and found that a substantial amount of NDHC was accumulated in tumor, as well as other organs including liver, spleen and kidneys (Supplementary Figure 10). As the size of NDHCs was around 100 nm, it probably accumulated in the tumor through a well-studied enhanced permeation and retention effect [21,22]. The antitumor efficacy of PTX-loaded NDHC delivery was then performed by future science group Nanoparticle-dendrimer hybrid nanocapsules for therapeutic delivery Research Article intravenous injection of PTX-loaded NDHCs, into C57BL6 mice bearing melanoma tumors.…”

A Quantitative Systems Pharmacology Perspective on Cancer Immunology

“…As an example, metastatic melanoma is arguably one of the hardest cancers to treat and has very few treatment options in the clinic. As an immunogenic cancer, it is known the immune system plays a role in progression of the disease [70]. Therefore, the immune system was targeted as a potential solution to molecular inhibitor resistance in metastatic melanoma and other cancers.…”

Nanomedicine in Melanoma: Current Trends and Future Perspectives

“…Morbidity and mortality indices are highly variable worldwide-being rare in nations of Asian and African origin and almost considered epidemic in countries of Caucasian predominance (2,3). When diagnosed early, as a localized cutaneous tumor, melanoma can be surgically removed with a good prognosis (4).…”

“…Temozolomide, a DTIC derivative, has the ability to cross the blood-brain barrier and is a first-line therapy for brain metastases (9). Recently, BRAF inhibitors (Vemurafenib, Dabrafenib) and MEK inhibitor (Trametinib) have been approved by the FDA for treating BRAF-mutated melanoma which is nearly found in 50% of cases (2). Immunotherapy is another promising treatment option in metastatic melanoma.…”

“…Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody (CTLA-4), and nivolumab and pembrolizumab, programmed death receptor 1 (PD-1) inhibitors, have been approved for use in the treatment of metastatic melanoma (10,11). However, despite these recent therapeutic breakthroughs, there are still some drawbacks including undesirable side effects, tumor chemoresistance, or even disease relapse (2,12). As cutaneous melanoma is a highly aggressive cancer (13), there is intense research focus on developing new, efficient drugs.…”