Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the members of the serine/threonine kinases. The group of tyrosine kinases is subdivided into subgroups: one of them includes the member of receptor tyrosine kinases (RTKs), while the other subgroup includes the member of non-receptor tyrosine kinases (NRTKs). Both these kinase groups function as an “on” or "off" switch in many cellular functions. NRTKs are enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions in response to extracellular signaling-dependent mechanisms. NRTK-mediated different cellular functions are regulated by kinase-dependent and kinase-independent mechanisms either in the cytoplasm or in the nucleus. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. This review deals with the structure and mechanistic role of NRTKs in tumor progression and resistance and their importance as therapeutic targets in tumor therapy.

Immunotherapy, particularly that based on blocking checkpoint proteins in many tumors, including melanoma, Merkel cell carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast (TNB cancer), renal cancer, and gastrointestinal and endometrial neoplasms, is a therapeutic alternative to chemotherapy. Immune checkpoint inhibitor (ICI)-based therapies have the potential to target different pathways leading to the destruction of cancer cells. Although ICIs are an effective treatment strategy for patients with highly immune-infiltrated cancers, the development of different adverse effects including cutaneous adverse effects during and after the treatment with ICIs is common. ICI-associated cutaneous adverse effects include mostly inflammatory and bullous dermatoses, as well as severe cutaneous side reactions such as rash or inflammatory dermatitis encompassing erythema multiforme; lichenoid, eczematous, psoriasiform, and morbilliform lesions; and palmoplantar erythrodysesthesia. The development of immunotherapy-related adverse effects is a consequence of ICIs’ unique molecular action that is mainly mediated by the activation of cytotoxic CD4⁺/CD8⁺ T cells. ICI-associated cutaneous disorders are the most prevalent effects induced in response to anti-programmed cell death 1 (PD-1), anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and anti-programmed cell death ligand 1 (PD-L1) agents. Herein, we will elucidate the mechanisms regulating the occurrence of cutaneous adverse effects following treatment with ICIs.

Prostate cancer (PCa) accounts for roughly 15% of diagnosed cancers among men, with disease incidence increasing worldwide. Age, family history and ethnicity, diet, physical activity, and chemoprevention all play a role in reducing PCa risk. The prostate is an exocrine gland that is characterized by its multi-functionality, being involved in reproductive aspects such as male ejaculation and orgasmic ecstasy, as well as playing key roles in the regulation of local and systemic concentrations of 5α-dihydrotestosterone. The increase in androgen receptors at the ventral prostate is the first elevated response induced by copulation. The regulation of prostate growth and function is mediated by an androgen-dependent mechanism. Binding 5-DHT to androgen receptors (AR) results in the formation of a 5α-DHT:AR complex. The interaction of the 5α-DHT:AR complex with the specific DNA enhancer element of androgen-regulated genes leads to the regulation of androgen-specific target genes to maintain prostate homeostasis. Consequently, ejaculation may play a significant role in the reduction of PCa risk. Thus, frequent ejaculation in the absence of risky sexual behavior is a possible approach for the prevention of PCa. In this review, we provide an insight into possible mechanisms regulating the impact of frequent ejaculation on reducing PCa risk.

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