Each year in the United States alone, almost 6 million people are treated for skin cancer [1] , and the number of new cases is growing [2] .

The most common types of skin cancer-basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), known as nonmelanoma skin cancers, are usually treatable, but treatment is expensive and can leave scars.

Early detection and prevention are crucial, but when skin cancer does develop, choosing the right treatment method is imperative.

Surgery is a medical specialty that uses manual and/or instrumental techniques with a knife to physically reach into the skin to treat pathological conditions. This type of approach has been adapted to excisional surgery for treating nonmelanoma and melanoma skin cancers. The objective of surgery of skin cancer aims to remove all the skin cancer and leave as much healthy skin tissue as possible.

In 1987, Bill Cham PhD, reported that plant derived glycoalkaloids solasodine glycosides, including solamargine, solasonine, mono- and di-glycosides of solasodine, known as BEC [4] [5] , induced remarkable anticancer effects with high therapeutic indices in cell culture [6] [7] , animals [8] , and humans [7] [9] [10] .

Since then, a plethora of further investigations have resulted in the placement of BEC and its individual components as very promising antineoplastic agents with vast potential to serve as targeted anticancer agents [7] . With BEC, solamargine accounts for 86% antineoplastic activity and solasonine accounts for 9%, whereas the mono- and di-glycosides of solasodine contribute 5% for antineoplastic activity. The anticancer activity of these glycoalkaloids is considered to be concerted and additive [11] .

The governing critical principle that determines the potency of antineoplastic activityof BEC is the plant sugar rhamnose that forms part of glycoalkaloid molecule [12] . By way of the rhamnose moiety, BEC recognizes and targets specific mutant endocytic endogenous lectin proteins located on cancer cell membranes that act as specific receptors for these glycoalkaloids. Normal non-cancer cells do not possess such specific receptors and are not affected by BEC.

After binding to these characterised specific receptors [7] [13] [14] , BEC is internalised by cell-receptor-mediated endocytosis. This is followed by the anticancer action of solasodine, the other moiety of the BEC glycoalkaloid, involving identifiable anticancer properties of a variety of biological pathways, including cell survival pathways [15] , tumour suppressor pathways [16] , lysosomal pathways [17] , mitochondrial pathways [18] , caspase activation pathways [19] , death receptor pathways [20] , protein kinase pathways [21] , and signal pathways that impede invasion/migration and multidrug resistance [7] .

BEC exhibits much higher cytotoxic effects on cancer cells than currently used antineoplastic agents such as vinblastine, vincristine, camptothecin, cisplatin, 5-fluorouracil, gemcitabine, epirubicin, cyclophosphamide, taxol and doxorubicin [7] .

Furthermore, the absolute concentrations of these drugs to obtain comparable efficacy as BEC, are in the order of 6 - 40 times higher [7] .

Moreover, the therapeutic index is much higher for BEC compared to other antineoplastic agents as shown in cell culture studies and animal studies [7] . The high therapeutic index of BEC translates to high safety margins. BEC is effective against over 20 types of cancers [7] and has curative properties in animals with terminal cancer [6] [7] . With the cell culture and animals studies, as little as 8 mg BEC/kg is required to kill the cancer cells and at this concentration BEC does not adversely affect normal non-cancer cells [8] .

In 1987 it was reported that topical application of a cream formulation containing high concentrations of BEC was effective in the treatment of the premalignant lesions actinic keratoses and malignant nonmelanoma skin cancers, BCC and SCC [7] [22] [23] [24] .

Optimizing the bioavailability of BEC with skin cancer cells at the concentration of BEC that is in the range of anticancer efficacy studies in cell culture and animals resulted in Curaderm, a very safe and effective treatment for skin cancers [7] [24] [25] [26] .

Double-blind, vehicle-controlled, randomized, paralleled, group studies and other multi-center clinical studies of Curaderm established that Curaderm, as a topical cream formulation, is a very effective, safe treatment with excellent cosmetic outcomes for actinic keratosis [27] [28] [29] , BCC [30] [31] [32] , SCC [32] [33] [34] and shows promise for stages 0 to 2 melanoma [35] [36] . Dermatologists, pathologists, oncologists and scientists contributed to various study designs with the Curaderm multicenter studies, ensuring the conclusion of statistical significances of efficacy and safety of Curaderm therapy, with small and very large skin cancer lesions. Clinical studies also showed that in cases whereby other well established treatment methods had failed in efficacy of treating skin cancer, subsequent treatment with Curaderm therapy was successful [30] [31] .

In 2018 Curaderm was registered as a medical device class 1 by the Decentralised European Authorisation Member State Mutual Recognition Procedure, for the indication “Topical treatment with keratolytic action, and antineoplastic activity in the treatment and healing of basal cell carcinoma of the skin”.

BEC in Curaderm are amphiphilic molecules that possess both hydrophilic and hydrophobic properties. The hydrophilic moiety, essentially the plant sugar rhamnose, binds to a mutant protein on malignant cancer cells (Figure 1). There are two types of binding of BEC on cancer cells, which are related to receptor affinity and numbers of receptors per cell [7] . Normal non-cancer cells do not contain the mutant protein receptors (Figure 2, Figure 3).

After binding and internalisation of BEC into cancer cells, the hydrophobic alkaloidal moiety, solasodine, triggers the cancer cell to commit suicide by the process of apoptosis (Figures 4-7) [24] .

BEC in Curaderm is very specific and effective for cancer cells. Figure 8 shows that BEC even distinguishes primary and metastatic cancer cells from benign and normal cells.

During early elimination of cancer cells with Curaderm, the lesion appears to become larger, followed by the reverse course until the lesion is completely removed and natural self-healing of the treated lesion ensues (Figure 9) [30] [32] .

Exceptional cosmetic outcomes with Curaderm treatment of various types of skin cancers are remarkable (Figures 10-13).

In order to understand the important differences between Mohs surgery and microscopic molecular-cellular therapy, comparisons of the two differing procedures are presented in Table 1.

Other important considerations with Mohs and Curaderm therapies

Mohs procedure takes place in an outpatient setting with the surgeon using a local anaesthetic to numb the area completely. The process takes between 4 and 6 hours. Some difficult or larger cases may take even longer. Reported efficacy is over 95% with low recurrence rates.

Curaderm is a self-administered home treatment without anaesthetics. Curaderm cream is applied topically twice daily to the lesion with an occlusive dressing. Duration of treatment depends on size, type, and location of skin cancer. Reported efficacy at 8 weeks of treatment is 78% and over 95% at 14 weeks of treatment with low recurrence rates.

Although the duration of treatment by Mohs procedure occurs within one day, this advantage is negated by the long wait time before treatment.

The mean wait time between referral to Mohs treatment is 215.8 days. Importantly, during this long wait time the lesion grows significantly by a factor of 1.41 [38] .

There is no wait time with Curaderm. Treatment can start on receiving Curaderm. Indeed, after commencement of Curaderm treatment it takes less time of Curaderm treatment with over 95% efficacy (14 weeks) than the waiting time (30.8 weeks) required for Mohs therapy.

Long waiting times have several deleterious effects. The larger the lesion, the more surgical removal of tissue is necessary with inherent cosmetic sequelae.

The cost of Mohs surgery varies depending on what body part is being treated. The face or scalp can cost between $1.000 - $5.000. Mohs on the hands and feet are usually in the range of $1.200 - $2.800 depending on the complexity of accessing deeper tissues.

The cost of treatment with Curaderm cream is less than 10% when compared with the cost of Mohs surgery.

Because of the modes of actions of surgery or microscopic-molecular-cellular Curaderm therapy, the cosmetic outcomes are very different. Surgery often requires a skin flap or skin graft with consequent scar formation and is dependent on the skill of the surgeon.

The cosmetic outcome with Curaderm is remarkable and is not dependent on human skill, but on the microscopic interaction of Curaderm with cancer cells.

Mohs surgery necessitates specially trained dermatologists whereas, Curaderm therapy requires only supervision of the treatment by general practitioners, translating to a much wider treatment availability.

Dermatologists should not be wary of a new treatment but should consider it as an addition to their expertise and ameliorate it as a supplementary new tool to complement their acumen and to extend patient care. The health and economic benefits of skin cancer intervention with Curaderm are transparent.

Natural or human intelligence resulted in Curaderm, a treatment for skin cancer. Much information was generated during its development that may, in combination with other treatment procedures, potentially guide to therapeutic applications, resulting in algorithms that may lead to not only diagnosis, but also, treatment of skin cancer by Artificial Intelligence (AI).

Excisional surgery aims to remove all the skin cancer cells and to reduce the amount of healthy skin tissue that is removed with the cancer. Although this is achievable, this procedure is considered suboptimal, and is being replaced with Mohs surgery, whereby it is considered that less healthy skin is removed resulting in improved cosmesis. Regardless, with Mohs surgery, skin flap or graft may still be required. These two surgical types of physical procedures result in scar tissue and are completely dependent on the multifaceted skills of the operators. However, although Mohs surgery is an overall improvement of excisional surgery, it falls short in removing all the cancer cells without removing any normal tissue cells.

With topical Curaderm therapy the specific anticancer action occurs at the microscopic molecular-cellular level without operator intervention, resulting in the removal of all cancer cells without removing any normal skin tissue.

Dr. Cham holds patent rights on BEC technology.

Cham, B.E. (2024) Gold Standard for Skin Cancer Treatment: Surgery (Mohs) or Microscopic Molecular-Cellular Therapy (Curaderm)? Journal of Cancer Therapy, 15, 33-47. https://doi.org/10.4236/jct.2024.152004