Twenty-five years with HER2 targeted therapy.

The development of trastuzumab is among the most significant cancer drug development projects in the 20th century. Trastuzumab became a gamechanger for the treatment of human epidermal growth receptor 2 (HER2) positive breast cancer, with a significant positive impact on disease recurrence and survival. The development of trastuzumab was the beginning of a new era of cancer drug development, which showed us the importance of understanding the molecular pathophysiology and drug mechanism of action.

Twenty-five years with companion diagnostics.

For decades, pharmacotherapy has been hampered by significant patient variability, and the inability to predict outcomes at the individual patient level has negatively affected its value. However, progress in molecular medicine has led to an increased understanding of the pathophysiology and mechanisms of action of drugs, thereby enabling the development of predictive biomarkers. Companion diagnostics (CDx) belongs to the group of predictive biomarkers, which the Food and Drug Administration (FDA) defines as an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product.

The Different Roles of MET in the Development and Treatment of Cancer.

This Special Issue features contributions from leading international researchers in the field of MET (hepatocyte growth factor (HGF) receptor) biology and therapeutics [...

The Potential of Trastuzumab Deruxtecan as a Tissue Agnostic Drug.

Background: Many modern anticancer drugs are designed to target specific molecular alterations harbored by the cancer. If a specific drug is able to target these alterations, regardless of the organ or tissue in which the cancer originates, it will often be characterized as a tissue- or tumor agnostic drug. According to the Food and Drug Administration (FDA), a tissue-agnostic drug refers to a drug that targets a specific molecular alteration across multiple cancer types, as defined by organ, tissue, or tumor type.

[Predictive biomarkers in medical treatment].

Use of predictive biomarkers plays a promising role in stratifying patients to a more effective medical treatment with less side effects. This review provides a brief overview in a Danish context of the potential of applying pharmacogenomics (PGx) including companion diagnostics (CDx) in daily clinical practice based on the current knowledge and regulation from the FDA and EMA, Summary of Product Characteristics (SPC), PharmGKB (pharmacogenomics knowledge resource providing clinical dosing guidelines) and partly promedicin.dk.

Missing Companion Diagnostic for US Food and Drug Administration-Approved Hematological and Oncological Drugs.

Within hematology and oncology, companion diagnostics (CDxs) play an increasing role in securing an optimal therapy for individual patients, and the US Food and Drug Administration (FDA) consider this type of assay essential for the safe and effective use of a corresponding therapeutic product. Most CDxs are developed prospectively using the drug-diagnostic codevelopment model, which normally secures the simultaneous approval of both drugs and diagnostics. A CDx assay is an important treatment decision tool that needs to be available simultaneously with the drug.

Companion Diagnostics and Predictive Biomarkers for MET-Targeted Therapy in NSCLC.

Dysregulation of the MET tyrosine kinase receptor is a known oncogenic driver, and multiple genetic alterations can lead to a clinically relevant oncogenesis. Currently, a number of drugs targeting MET are under development as potential therapeutics for different cancer indications, including non-small cell lung cancer (NSCLC). However, relatively few of these drugs have shown sufficient clinical activity and obtained regulatory approval.

Oncology drug-companion diagnostic combinations.

With the development of trastuzumab for metastatic breast cancer a new era began in cancer drug development. The drug-diagnostic codevelopment model with its clinical enrichment trial design has enabled development of target specific drugs for molecular defined subsets of patients. Since the simultaneous approval of trastuzumab and the HercepTest in 1998, the number of FDA-approved drug-companion diagnostic combinations within oncology and hematology have steadily increased.

A Companion Diagnostic With Significant Clinical Impact in Treatment of Breast and Gastric Cancer.

The development of trastuzumab (Herceptin) was one of the most significant cancer drug development projects of the 20th century. Not only was it a scientific and medical achievement but it also paved the way for the drug-diagnostic codevelopment model, where a predictive biomarker assay is developed in parallel to the drug. One of the challenges in the development of trastuzumab was to select the right patient population likely to respond and here, it was critical to have access to an accurate, robust and reliable assay for detection of HER2 overexpression in tumors.

An update on companion and complementary diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC.

: Development within molecular medicine has given us an increased understanding of the pathophysiology of malignant diseases. This understanding has been the key to a development of a number of new effective target-specific drugs, including the PD-1/PD-L1 checkpoint inhibitors.: This review will focus on the clinical validation and utility of the commercially available IHC PD-L1 expression assays linked to the different PD-1/PD-L1 checkpoint inhibitors indicated for treatment of NSCLC.

The current landscape of the FDA approved companion diagnostics.

Predictive biomarker is an important element in the realization of precision medicine and with the introduction of the drug-diagnostic codevelopment model, the number of regulatory approved companion diagnostics (CDx) have steadily increased. This short perspective is based on an analysis of the FDA List of Cleared or Approved Companion Diagnostic Devices and focus on the biomarkers, drugs, clinical indications, analytical platforms, regulatory paths and status related to the different assays. By the end of 2020, the total number of CDx assays approved by the FDA had reached 44.

deletion is a frequent event in gastric/gastroesophageal junction/esophageal cancer: a cross-sectional analysis of gene status and signal distribution in 1,580 patients.

Background: gene aberrations are found in several human cancers including gastric, ovarian and lung. In a large multinational cohort of patients with gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma we assessed the MET status with respect to amplification and deletion and correlate the results with the phenotypical gene signal distribution pattern.

Methods: Tissue specimens from 1,580 patients were analyzed using a novel fluorescence in situ hybridization (FISH) assay employing a /CEN-7 IQFISH Probe Mix.

Predictive biomarkers and clinical evidence.

Predictive biomarkers play an important role in our efforts to individualize pharmacotherapy, and within recent years, a number of different types of assays have been introduced. These biomarkers may potentially support the selection and dosage of specific drugs in order to maximize efficacy and minimize adverse reactions in the individual patient. However, in many instances, the scientific and clinical evidence is insufficient to support the prescribing decision.

Site-agnostic biomarker-guided oncology drug development.

Introduction: Advances within molecular diagnostics have enabled us to identify a number of oncogenic drivers across different cancers. Many cancers can now be divided into subgroups based on molecular characteristics, and an increasing number of targeted anticancer drugs have been developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. With the recent approval of entrectinib, larotrectinib, and pembrolizumab for site-agnostic indications, biomarker-guided drug development has entered into a new phase.

A paradigm shift in biomarker guided oncology drug development.

Over the past couple of decades, biomarker driven enrichment clinical trials have proven to be an important tool in clinical drug development, especially for targeted anti-cancer drugs. By the end of 2018, more than 30 drugs have been developed in conjunction with a biomarker test and have a regulatory approved companion diagnostic linked to their use. With the recent approval of larotrectinib (Vitrakvi, Loxo Oncology/Bayer) for patients with neurotrophic receptor tyrosine kinase () gene fusion and pembrolizumab (Keytruda, MSD) for microsatellite instability-high (MSI-H) and mis-match-repair-deficient (dMMR) positive patients, we are experiencing a paradigm shift in biomarker guided drug development.

Twenty Years with Personalized Medicine: Past, Present, and Future of Individualized Pharmacotherapy.

On April 16, 1999, a short article appeared in entitled "New Era of Personalized Medicine: Targeting Drugs for Each Unique Genetic Profile," and here, the public was introduced to the term "personalized medicine" for the first time. A few months after publication of the article, it was reprinted in . The article describes the formation of the Single Nucleotide Polymorphisms Consortium, which was established as a collaboration between a number of major pharmaceutical companies and several academic research institutions, with support from the Wellcome Trust Foundation.

Detection of amplification in gastroesophageal tumor specimens using IQFISH.

Background: The gene mesenchymal epithelial transition factor () is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. is found to be amplified in several human cancers including gastroesophageal cancer.

Methods: Here we report the amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, /CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay].