Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma

Abstract

Melanoma is one of the most severe cancerous diseases. The cells employ multiple signaling pathways, such as ERK, HGF/c-MET, WNT, and COX-2 to cause the cell proliferation, survival, and metastasis. Treatment of melanoma, including surgery, chemotherapy, immunotherapy, radiation, and targeted therapy, is based on 4 major or 11 substages of the disease. Fourteen drugs, including dacarbazine, interferon α-2b, interleukin-12, ipilimumab, peginterferon α-2b, vemurafenib, trametinib, talimogene laherparepvec, cobimetinib, pembrolizumab, dabrafenib, binimetinib, encorafenib, and nivolumab, have been approved by the FDA for the treatment of melanoma. All of them are in conventional dosage forms of injection solutions, suspensions, oral tablets, or capsules. Major drawbacks of the treatment are side effects of the drugs and patients' incompliance to them. These are consequences of high doses and long-term treatments for the diseases. Currently more than 350 NCI-registered clinical trials are being carried out to treat advanced and/or metastatic melanoma using novel treatment methods, such as immune cell therapy, cancer vaccines, and new therapeutic targets. In addition, novel delivery systems using biomaterials of the approved drugs have been developed attempting to increase the drug delivery, targeting, stability, bioavailability, thus potentially reducing the toxicity and increasing the treatment effectiveness. Nanoparticles and liposomes have been emerging as advanced delivery systems which can improve drug stability and systemic circulation time. In this review, the most recent findings in the options for treatment and development of novel drug delivery systems for the treatment of melanoma are comprehensively discussed.

Self-supplying Cu2+ and H2O2 synergistically enhancing disulfiram-mediated melanoma chemotherapy

“…[1][2][3][4][5][6][7][8] Surgery shows very limited efficacy for advanced melanoma, and classic treatments such as chemotherapy and targeted therapy are very costly and have side effects. [9][10][11] Herein, a new treatment is proposed for advanced melanoma using clinically approved "old drugs", 12,13 with reduced clinical trial time and high biosafety.…”

Programmed cell death‐1 blockade therapy in melanoma: Resistance mechanisms and combination strategies

“…These kinds of drugs not only dramatically improve the prognosis, but also alter the traditional clinical practice patterns for melanoma. [1][2][3][4] Programmed cell death-1 (PD-1) is a well-known immune checkpoint molecule that can negatively regulate the magnitude of the immune response. In physiological conditions, PD-1 is able to restrict over-activation of some effector cells by interacting with its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2), as a self-protection mechanism.…”

“…Several novel and promising treatments for melanoma are recently in use; these include BRAF inhibitors, c‐Kit inhibitors, mitogen‐activated extracellular signal‐regulated kinase (MEK) inhibitors, and immune checkpoint inhibitors. These kinds of drugs not only dramatically improve the prognosis, but also alter the traditional clinical practice patterns for melanoma 1–4 …”

LINC01296 promotes proliferation of cutaneous malignant melanoma by regulating miR-324-3p/MAPK1 axis

“…Thus, early surgical excision is the optimal treatment option for CMM and is recognized as the most significant and promising therapy [ 7 ]. CMM is mostly progressed from sputum or pigmented plaque, and the underlying mechanisms of CMM are multifactorial and complex, constituting a complicated net of multiple risk factors, ultimately leading to the uncontrolled cancer cell growth [ 8 ]. Differentially expressed genes might have a role in the malignancy of CMM, which might serve as therapeutic targets for CMM [ 4 , 9 ].…”