Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches

Abstract

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.

Keywords: Combination therapy; Etiology; Melanoma; Nanotechnology; Non-melanoma; Phytocompounds; Skin cancer; Targeted therapy; Toxicity.

Fig. 1

Illustration of different molecular pathways involved in Basal cell carcinoma. Adapted with permission from [50]

Fig. 2

Representation of therapeutic landscapes involved in Cutaneous cell carcinoma. Adapted with permission from [56]

Fig. 3

Illustrates different types of Skin cancers

Fig. 4

Diagrammatic representation of the detailed mechanism of tumor vascularization

Fig. 5

Procedure for Mohs Microscopic surgery used for the removal of the tumor from the skin. Adapted with permission from [141]

Fig. 6

An illustration of the effector mechanism in photodynamic therapy. 1) Activation of the photosensitizer by external light of a specific wavelength results in the singlet state, which is followed by the creation of reactive oxygen species (ROS), which is the main cause of the apoptosis of tumor cells. 2) Photodynamic therapy activates the immune system, releasing inflammatory mediators like IL-6, IL-1, and TNF-alpha, heat shock protein (HSP), and DAMPs (Damage Associated Molecular Patterns), which cause tumor cells to die

Fig. 7

Illustration of cell types, processes, immunotherapy, and their effect on the tumor after intratumoral administration. Adapted with permission from [207]

Fig. 8

Representation of different approaches for the management of skin cancer

Fig. 9

Physical methods employed for enhancing the penetration ability of the drug

Fig. 10

SEM image of Me300 melanoma cells in which A) represents cells not exposed to iron oxide nanoparticles while B and C) represent treatment groups exposed to amino ultra-small superparamagnetic iron oxide nanoparticles [250], (D) influence of @BSA-RF@RGD on AuNRs uptake [251], (E) FESEM and TEM images of ZnO nanoparticles in which Low magnification FESEM image, (F) high-magnification FESEM image, (G) Low magnification TEM image of ZnO, and (H) high-magnification TEM image of ZnO showing distance between lattice fringes around 0.265 nm [252], (I and J) TEM and FESEM image of cerium oxide nanoparticles respectively. Adapted with permission from [253]

Fig. 11

A) Process of fabrication of cancer cell membrane camouflaged Dacarbazine loaded porous silica nanoparticles and B) Induction of antitumor immune response by DTIC@CMSN combined with aPD1. Adapted with permission from [281]

Fig. 12

illustration of A) fabrication process of Gelatin/PVA solution, PLGA-DOX loaded nanoparticle consisting microbot hydrogel, B) Targeting and treatment process of microbot hydrogel with the aid of EMA and NIR for local cancer treatment. Adapted with permission from [383]