Insights into the Use of CDK 4/6 Inhibitors in Patients with HR-positive Advanced or Metastatic Breast Cancer

Hormone receptor(HR)-positive breast cancer(BC)is the most common subtype of BC and some patients with such tumors experience recurrences.Endocrine-based therapy(ET)(e.g.,tamoxifen,aromatase inhibitors(AIs),and fulvestrant)that has improved outcomes in such patients represents the initial therapy for women with HR-positive/human epidermal growth factor receptor 2(HER2)-negative BC(considering no evidence of visceral crisis).However,the resistance to ET can occur in almost 50%of HR-positive BCs.In order to improve outcomes of patients with HR-positive metastatic BC,new treatment strategies are required.One such therapy is the new class of medications,cyclin-dependent kinase(CDK)4/6 inhibitors,that have improved the outcomes in such patients(both endocrine-sensitive and endocrine-resistant).This article presents evidence from the main clinical trials,which led to the approval of palbociclib,ribociclib,and abemaciclib.These three CDK 4/6 inhibitors have shown a significant improvement of the progression-free survival(PFS)in patients with HR-positive/HER2-negative metastatic BC when used in combination with selected ETs.In addition,some important patient management considerations,when choosing a particular CDK 4/6 inhibitor for an individual patient are presented.Furthermore,a need to find biomarkers for CDK 4/6 inhibitor sensitivity,efficacy,and resistance,to be able to precisely select the best patientcandidates for this treatment is highlighted.

Interrelations Between Psychological Stress and Cancer-Deciphering Molecular Signals in the Tumor Microenvironment

Current research has revealed some links between psychological stress and cellular mutation,neoplastic proliferation and metastasis in patients with cancer.In stressful situations,the stress-related neuroendocrine mediators(e.g.,catecholamines,and glucocorticoids(GSs))are being secreted,via stimulation of the sympathetic nervous system(SNS),and the hypothalamic-pituitaryadrenocortical(HPA)axis.Catecholamine may affect the malignant progression,since they can regulate various cellular signaling pathways,via adrenergic receptors(ARs)that are expressed by different types of neoplastic cells.The ARs increase the proliferation and invasive potential of such cells,and change their“behavior”in the tumor microenvironment.Similarly,cortisol and its glucocorticoid receptors(GRs)can promote stress-induced malignant growth and metastasis.Maladaptation to stressful situations,often relevant to the cancer diagnosis and treatment,may accelerate tumor growth and spread(e.g.,via inflammation,angiogenesis,and migration).Studies have shown that psychological interventions can be helpful for adaptation to adverse circumstances during the therapeutic process in patients with cancer.This mini-review will address some interrelations between psychological stress and cancer.It will discuss how the receptor-mediated signaling pathways may lead to cancer initiation,propagation,and spread.In addition,it will describe a supportive role of the stress reduction strategies,for example,in patients with breast cancer(BC).