NOVEL SYNTHETIC APPROACHES FOR THE TREATMENT OF MALIGNANT MELANOMA UNDER CLINICAL TRIAL

ABOUT AUTHORS:
Tara Shankar Basuri^1*, Ishvar Parmar¹, Vishal Modi², Virag Shah³, Niyatee Thakur⁴
SSR College of pharmacy, Silvassa,
U.T of Dadra & Nagar Haveli-396230
*tbasuri@gmail.com

ABSTRACT
Malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on novel synthetic and herbal drugs for malignant melanoma treatment, by a single or combinational agent approach. These molecules are widely used by the oncologists for the treatment of this type of cancer. So this review can help to the public to aware the malignant melanoma and its treatment and novel target for its treatment.

REFERENCE ID: PHARMATUTOR-ART-1804

INTRODUCTION
Melanoma¹ is a cancer that starts in a certain type of skin cell. Melanoma is a cancer that begins in the melanocytes. Other names for this cancer include malignant melanoma and cutaneous melanoma. Because most melanoma cells still make melanin, melanoma tumors are usually brown or black. But some melanomas do not make melanin and can appear pink, tan, or even white. Melanomas² can occur anywhere on the skin, but they are more likely to start in certain locations. The trunk (chest and back) is the most common site in men. The legs are the most common site in women. The neck and face are other common sites.Skin cancer is usually a result of too much exposure to the sun. While skin cancer is the most common form of cancer, many types are both preventable and treatable. Having darkly pigmented skin lowers your risk of melanoma at these more common sites, but anyone can develop this cancer on the palms of the hands, soles of the feet, and under the nails. Melanomas in these areas account for more than half of all melanomas in African Americans but fewer than 1 in 10 melanomas in whites.

Melanomas can also form in other parts of your body such as the eyes, mouth, and genitals, but these are much less common than melanoma of the skin. Melanoma is much less common than basal cell and squamous cell skin cancers, but it is far more dangerous. Like basal cell and squamous cell cancers, melanoma is almost always curable in its early stages. But it is much more likely than basal or squamous cell cancer to spread to other parts of the body if not caught early.

Figure 1: A Melanoma

Other Skin Cancers
Skin cancers that are not melanomas are sometimes grouped as non-melanoma skin cancers because they develop from skin cells other than melanocytes. They tend to behave very differently from melanomas and are often treated in different ways.

Non-melanoma skin cancers include basal cell and squamous cell cancers. They are by far the most common skin cancers, and actually are more common than any other form of cancer. Because they rarely spread (metastasize) to other parts of the body, basal cell and squamous cell skin cancers are less worrisome and are treated differently from melanoma. Merkel cell carcinoma is an uncommon type of skin cancer that is sometimes harder to treat.

There are five different types of skin cancer:

Basal cell carcinoma³ is the most common form and accounts for 90% of all skin cancers. It starts in the basal cells, at the bottom of the outer skin layer and is caused by long-term exposure to sunlight. It is the most easily treated.
Squamous cell carcinoma⁴ is the second most common type. It starts in the outer skin layer, eventually penetrating the underlying tissue if not treated. It is easily treated when found early, but in a small percentage of cases this cancer spreads to other parts of the body.
Malignant melanoma is the most serious type of skin cancer⁵ and is responsible for the most deaths. However, it can be cured if it is diagnosed and removed early. Melanoma starts in moles or other growths on normal skin.
Kaposi's sarcoma (KS) is caused by a virus in the herpes family. An aggressive AIDS-related form affects about one third of people with AIDS. A more slow-growing form occurs in elderly men of Italian or Jewish ancestry.

Chemotherapy for melanoma skin cancer
Chemotherapy (chemo) uses drugs that kill cancer cells. The drugs are usually injected into a vein or taken by mouth as a pill. They travel through the bloodstream to all parts of the body and attack cancer cells that have already spread beyond the skin to lymph nodes and other organs. Because the drug reaches all areas of the body, it is called a systemic therapy.

Chemo is often used to treat advanced melanoma. Although it is usually not as effective in melanoma as it is in some other types of cancer, chemo may relieve symptoms or extend survival for some patients.

Doctors give chemotherapy in cycles; with each period of treatment followed by a rest period to allow the body time to recover. Each chemotherapy cycle typically lasts for a few weeks.

Several clinical trials have been done may be used to treat melanoma:
BLEOMYCIN:
Bernd et al⁶ found that Bleomycin enhances the tyrosinase activity of human malignant melanoma cells in culture. By application of bleomycin fine pigmentations on basal cell layers will appear in irritated parts of the skin. Therefore we investigated the effect of bleomycin on the tyrosinase activity

CARBOPLATIN
Rassnick et al⁷ found the use of carboplatin for treatment of dogs with malignant melanoma. Carboplatin had activity against macroscopic spontaneously occurring malignant melanomas in dogs and should be considered as an adjunctive treatment for microscopic local or metastatic tumors. Gastrointestinal toxicosis was associated with body weight. Because small dogs are more likely to have adverse gastrointestinal effects, gastrointestinal protectants should be considered for these patients.

CATECHINS
Singh et al found that Green Tea⁸ Catechins reduce invasive potential of human melanoma cells by targeting COX-2, PGE₂ receptors and epithelial-to-mesenchymaltransition.

CISPLATIN
Feliu at al⁹ found treatment of metastatic malignant melanoma with cisplatin plus tamoxifen.

CURCUMIN
Bill et al found that curcumin¹⁰ induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines. Curcumin has potential as a chemopreventative and chemotherapeutic agent, but its interactions with clinically relevant cytokines are poorly characterized.

DACARBAZINE
Pectasides et al¹¹ found the treatment of metastatic malignant melanoma with dacarbazine.

EPIGALLOCATECHIN-3-GALLATE
Ellis at al¹² found that Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion. Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties.

EVAROLIMUS¹³

RESVERATROL
Fuggetta et al found the in vitro antitumour activity¹⁴ of resveratrol in human melanoma cells sensitive or resistant to temozolomide. Resveratrol, a polyphenol present in many plant species, exhibits a wide range of biological and pharmacological activities both in.vitro and in vivo

TEMOZOLOMIDE
Daponte et al¹⁵ used Temozolomide and cisplatin in avdanced malignant melanoma. Temozolomide (TMZ) is an oral alkylating agent; it produces DNA methyl adducts, which are removed by the DNA repair enzyme

VEMURAFENIB
Amaria et al¹⁶ reviewed that advanced melanoma has a poor prognosis due to its resistance to traditional chemotherapeutics, leading to the search for alternative treatment approaches.

VINBLASTINl:
Bajetta et al postulated the treatment of advanced malignant melanowith vinblastine¹⁷, bleomycin, and cisplatin.

VINCRISTINE
Byrne founded that vincristine¹⁸ useful in the treatment of malignant melanoma. Patients with advanced malignant melanoma were randomly assigned to treatment with cylcophosphamide and vincristine (CV) or cyclophosphamide, vincristine, and procarbazine (CVP).

VINDESINE
Quagliana et al¹⁹ founded vindesine useful in treatment in malignant melanoma. A phase II study using vindesine (3 mg/ml by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma.

ZENIPLATIN
Aamdal et al¹² reviewed that the antitumor activity of zeniplatin, a third-generation, water-soluble platinum compound that has shown broad preclinical antitumor activity and no significant nephrotoxicity in phase I trials, was tested in patients with advanced malignant melanoma and advanced renal cancer.

CONCLUSION
The future of medicinal chemistry awaits an outstanding era of potent molecules to come in line. The skin cancer crises have been evolving challenges and this review has surfaced novel strategies come out them. In this work describes the detail structure and mechanism of novel molecules. Hopefully these new strategies will help the future pharmacist to avert malignant melanoma.

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