Overview of Current Targeted Anti-Cancer Drugs for Therapy in Onco-Hematology.

The upgraded knowledge of tumor biology and microenviroment provides information on differences in neoplastic and normal cells. Thus, the need to target these differences led to the development of novel molecules (targeted therapy) active against the neoplastic cells' inner workings. There are several types of targeted agents, including Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA (iRNA) molecules and microRNA. In the clinical practice, these new medicines generate a multilayered step in pharmacokinetics (PK), which encompasses a broad individual PK variability, and unpredictable outcomes according to the pharmacogenetics (PG) profile of the patient (e.g., cytochrome P450 enzyme), and to patient characteristics such as adherence to treatment and environmental factors. This review focuses on the use of targeted agents in-human phase I/II/III clinical trials in cancer-hematology. Thus, it outlines the up-to-date anticancer drugs suitable for targeted therapies and the most recent finding in pharmacogenomics related to drug response. Besides, a summary assessment of the genotyping costs has been discussed. Targeted therapy seems to be an effective and less toxic therapeutic approach in onco-hematology. The identification of individual PG profile should be a new resource for oncologists to make treatment decisions for the patients to minimize the toxicity and or inefficacy of therapy. This could allow the clinicians to evaluate benefits and restrictions, regarding costs and applicability, of the most suitable pharmacological approach for performing a tailor-made therapy.

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas.

The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.