Until today, numerous studies evaluated the topic of anthocyanins and various types of cancer, regarding the anthocyanins’ preventative and inhibitory effects, underlying molecular mechanisms, and such. However, there is no targeted review available regarding the anticarcinogenic effects of dietary anthocyanins on skin cancers. If diagnosed at the early stages, the survival rate of skin cancer is quite high. Nevertheless, the metastatic form has a short prognosis. In fact, the incidence of melanoma skin cancer, the type with high mortality, has increased exponentially over the last 30 years, causing the majority of skin cancer deaths. Malignant melanoma is considered a highly destructive type of skin cancer due to its particular capacity to grow and spread faster than any other type of cancers. Plants, in general, have been used in disease treatment for a long time, and medicinal plants are commonly a part of anticancer drugs on the market. Accordingly, this work primarily aims to emphasize the most recent improvements on the anticarcinogenic effects of anthocyanins from different plant sources, with an in-depth emphasis on melanoma skin cancer. We also briefly summarized the anthocyanin chemistry, their rich dietary sources in flowers, fruits, and vegetables, as well as their associated potential health benefits. Additionally, the importance of anthocyanins in topical applications such as their use in cosmetics is also given.

Pentacyclic triterpenoids (TTs) represent a unique family of phytochemicals with interesting properties and pharmacological effects, with some representatives, such as betulinic acid (BA) and betulin (B), being mainly investigated as potential anticancer molecules. Considering the recent scientific and preclinical investigations, a review of their anticancer mechanisms, structure-related activity, and efficiency improved by their insertion in nanolipid vehicles for targeted delivery is presented. A systematic literature study about their effects on tumor cells in vitro and in vivo, as free molecules or encapsulated in liposomes or nanolipids, is discussed. A special approach is given to liposome-TTs and nanolipid-TTs complexes to be linked to microbubbles, known as contrast agents in ultrasonography. The production of such supramolecular conjugates to deliver the drugs to target cells via sonoporation represents a new scientific and applicative direction to improve TT efficiency, considering that they have limited availability as lipophilic molecules. Relevant and recent examples of in vitro and in vivo studies, as well as the challenges for the next steps towards the application of these complex delivery systems to tumor cells, are discussed, as are the challenges for the next steps towards the application of targeted delivery to tumor cells, opening new directions for innovative nanotechnological solutions.

Anthocyanins are water-soluble pigments present in fruits and vegetables, which render them an extensive range of colors. They have a wide distribution in the human diet, are innocuous, and, based on numerous studies, have supposed preventive and therapeutical benefits against chronic affections such as inflammatory, neurological, cardiovascular, digestive disorders, diabetes, and cancer, mostly due to their antioxidant action. Despite their great potential as pharmaceutical applications, they have a rather limited use because of their rather low stability to environmental variations. Their absorption was noticed to occur best in the stomach and small intestine, but the pH fluctuation of the digestive system impacts their rapid degradation. Urine excretion and tissue distribution also occur at low rates. The aim of this review is to highlight the chemical characteristics of anthocyanins and emphasize their weaknesses regarding bioavailability. It also targets to deliver an update on the recent advances in the involvement of anthocyanins in different pathologies with a focus on in vivo, in vitro, animal, and human clinical trials.

The development of therapies that target cancer stem cells (CSCs) and bulk tumors is both crucial and urgent. Several signaling pathways, like Notch and Hedgehog (Hh), have been strongly associated with CSC stemness maintenance and metastasis. However, the extensive crosstalk present between these two signaling networks complicates the development of long-term therapies that also minimize adverse effects on healthy tissues and are not overcome by therapy resistance from CSCs. The present work aims to overview the roles of Notch and Hh in cancer outburst and the intersection of the two pathways with one another, as well as with other networks, such as Wnt/β-catenin, TGF, and JAK/STAT3, and to explore the shaping of the tumor microenvironment (TME) with specific influence on CSC development and maintenance.

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure to UV radiation, aging populations, and exposure to teratogen agents. However, diagnosis is more precise, and the increased number of new cases is related to the improved diagnosis tools. Despite better early diagnosis and better therapies, melanoma has remained a significant public health challenge because of its aggressive behavior and high potential for metastasis. In 2020, cutaneous melanoma constituted approximately 1.3% of all cancer deaths that occurred within the European Union, thereby highlighting the necessity for effective prevention, timely diagnosis, and sustainable treatment measures, especially as a growing number of cases occur among younger patients. Melanoma is regarded as one of the most inflamed cancers due to its high immune cell presence and strong response to immunotherapy, fueling the need for development of immune-driven innovative treatments. Approved therapies, including immune checkpoint inhibitors (e.g., anti-PD-1 and anti-CTLA-4), have notably improved survival rates in melanoma. However, the limitations of the PD-1/PD-L1 and CTLA-4 axes inhibitors, such as low response rates, treatment resistance, and toxicity, have driven the need for continued research and advancements in treatment strategies. Current clinical trials are exploring various combinations of immune checkpoint inhibitors with costimulatory receptor agonists, chemotherapy, targeted therapies, and other immunotherapies, with the goal of improving outcomes and reducing side effects for melanoma patients. Emerging approaches, including adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) and oncolytic virotherapy, are showing promise. While CAR-T cell therapy has been less successful in melanoma compared to blood cancers, ongoing research is addressing challenges like the tumor microenvironment and antigen specificity. This review provides an overview of the requirement for advances in these medications, to mark a significant step forward in melanoma management, set to bring a fresh breath of hope for patients.

Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs). Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade. While commonly involved in embryogenesis and adult tissues homeostasis, the dysregulation of the Wnt pathway has direct correlations with tumorigenesis, metastasis, and drug resistance. The development of therapies that target CSCs and bulk tumors is both crucial and urgent. However, the extensive crosstalk present between Wnt and other signaling networks (Hedgehog and Notch) complicates the development of efficient long-term therapies with minimal side-effects on normal tissues. Despite the obstacles, the emergence of Wnt inhibitors and subsequent modulation of the signaling pathways would provide dynamic therapeutic approaches to impairing CSCs and reversing resistance mechanisms.