Purpose of Review We aim to provide a comprehensive analysis of hypercoagulability in individuals affected by COVID-19. Our goal is to describe the hypercoagulable state related to the infection and provide guidance regarding the possible benefits of anti-coagulation with the support of evidence from current literature. Recent Findings The incidence of thrombotic disease in individuals affected by COVID-19 is reported as high as 31%. A significant mortality benefit has been observed with the use of therapeutic anticoagulation in high-risk individuals. Literature supports the use of scoring systems, such as the sepsis-induced coagulopathy score, to risk-stratify individuals who might benefit from anticoagulation. Summary COVID-19-induced hypercoagulability has been demonstrated to play a significant role in overall COVID-19 outcomes. Current literature shows promising evidence with the use of therapeutic anticoagulation in high-risk individuals. Further studies are needed to better analyze the risks and benefits of anticoagulation in this specific patient population.

Oncogenic gene fusions are hybrid genes that result from structural DNA rearrangements, leading to unregulated cell proliferation by different mechanisms in a wide variety of cancer. This has led to the development of directed therapies to antagonize a variety of mechanisms that lead to cell growth or proliferation. Multiple oncogene fusions are currently targeted in lung cancer treatment, such as those involving ALK, RET, NTRK and ROS1 among many others. Neuregulin (NRG) gene fusion has been described in the development of normal tissue as well as in a variety of diseases, such as schizophrenia, Hirschsprung’s disease, atrial fibrillation and, most recently, the development of various types of solid tumors, such as renal, gastric, pancreatic, breast, colorectal and, more recently, lung cancer. The mechanism for this is that the NRG1 chimeric ligand leads to aberrant activation of ERBB2 signaling via PI3K-AKT and MAPK cellular cascades, leading to cell division and proliferation. Details regarding the incidence of these gene rearrangements are lacking. Limited case reports and case series have evaluated their clinicopathologic features and prognostic significance in the lung cancer population. Taking this into account, NRG1 could become a targetable alteration in selected patients. This review highlights how the knowledge of new molecular mechanisms of NRG1 fusion may help in gaining new insights into the molecular status of lung cancer patients and unveil a novel targetable molecular marker.

Biologic agents have revolutionized the management of serious health conditions in the last two decades. The use of “targeted therapy” brings not only better progression free survivals and overall survivals, but also better toxicity profiles and quality of life benefits, compared to empirical palliative chemotherapy. However, given the high cost associated with biologic drugs and the sharp increases in biologic drug utilization, this drug category has significantly raised healthcare cost over the years. A similar phenomenon was previously experienced with branded simple chemical compound drugs, including chemotherapeutic agents, which was largely mitigated by the introduction of a generic approval pathway, decreasing the costs of the drugs, making them more affordable, given to the increase in competition among the drug makers. A similar opportunity presents years later with the completion of the full patent exclusivity period of many biologics. However, the ending of patent exclusivity, although enables more market competition, does not guarantee market penetration. Stakeholders, such as patients, providers and payers, must build trust and confidence in the science of biosimilars and the product specific studies leading to FDA approval in order to incorporate these products to practice and enable the biosimilar market at large to reach the potential to significantly contribute to reductions in drug cost. Dissemination of scientific and emerging biosimilar evidence is paramount in order to support stakeholder informed decision making and enable each to benefit from expanded treatment options. This paper describes the biosimilar development, approval process, and reviews a number of challenges with the marketing implementation of biosimilars.

Liquid biopsies have evolved as a promising non-invasive technology for cancer diagnosis and treatment, as they provide a comprehensive analysis of tumor-derived biomarkers. Prospective multicenter studies have shown the efficacy of liquid biopsies, including circulating tumoral DNA (ctDNA) and more recently cfRNA analysis, in identifying biomarkers for targeted therapies in patients with non-small cell lung cancer (NSCLC). In addition, studies have demonstrated a reduced time to treatment initiation when liquid biopsies are used in conjunction with or in lieu of tissue genotyping. Although liquid biopsies hold excellent potential, there are several obstacles to overcome, including technical limitations, standardization of methodologies, and cost-effectiveness. However, ongoing research and technological advances are conquering these obstacles, resulting in enhanced performance and dependability of liquid biopsy assays. To maximize the clinical utility of liquid biopsies, it is necessary to continue research, validation studies, and standardization initiatives. The incorporation of liquid biopsies into standard clinical practice has the potential to revolutionize the diagnosis and treatment of cancer. These noninvasive tests not only are a great tool for diagnosis but also allow real-time monitoring, guide treatment decisions, and enhance patient outcomes. As the costs of next-generation sequencing (NGS) declines, global access to liquid biopsies is anticipated to increase. Liquid biopsies arrived in the clinical practice after we were familiar with the analysis of genetic aberrations in tissue by next generation sequencing (NGS) that is considered the standard of care in new patients with the diagnosis of metastatic non-small cell lung cancer (NSCLC) and sometimes are used now as complement of tissue analysis or only when there is not enough tissue available. We already have done enough studies that show the non-inferiority and equivalence of liquid biopsies with molecular tissue testing. This article explores recent studies that demonstrate the clinical utility and potential of liquid biopsies in oncology including the possibility to use them at the same time of tissue analysis and the comparison of both with the advantage for the patient to get an earlier result due to the shorter turnaround time of liquid biopsies.

Non-small cell lung cancer (NSCLC) is operated commonly by diverse genetic alterations, and oncogenic fusions represent a significant therapeutic role. Common fusions include ALK, ROS1, RET, and NTRK, signaling pathways in tumorigenesis. Recent advances in investigating tumor molecular biology include underlying fusions, including chromosomal rearrangements, highlighting their role as oncogenic drivers. The development of targeted therapies, such as tyrosine kinase inhibitors (TKIs), has impacted most patients’ NSCLC treatment. Despite the greater profiles, such as remarkable efficiency and tolerable side effects compared to traditional chemotherapy, challenges, such as acquired mutations, lead to more ongoing research-optimized future NSCLC therapies.

Recent years has seen the discovery and description of genetic alterations responsible for oncogenesis in a wide variety of cancers, together with the finding that some markers are actionable and can be targeted by medications. Such developments have enabled cancer treatments to evolve from empirical palliative chemotherapy, with low chances of response or curative intent in most types of cancers, to targeted therapy, with some studies showing promising results in terms of improved overall response rates, overall survival and quality of life, although, like all new groups of medications, with specific adverse effect profiles. This treatment evolution is a major development in cancer therapy. Tumors were originally classified as solid or liquid tumors based on their location in the human body (solid organs or blood), which evolved into the medical specialties of medical oncology and clinical hematology, respectively. Subsequently, tumors were classified by the organ they originate from, in the belief that the origin of the tumor would guide its biological behavior and would faciliate understanding of their mechanism of spread and, potentially, of the best treatment approach. Although this latter approach has achieved some success over the many years it has been applied, there have been major disappointments, particularly in lung cancers for which palliative chemotherapy has only been able to provide a median survival of around 1 year and a complete remission rate of < 5%. We are now understanding that this concept of cancer pathophysiology is more complex, but also potentially simple, and that one or several molecular aberrations are probably responsible for the origin of each cancer. Various molecular alterations have been described, although the relevance of each alteration is not yet fully understood. In this article, we highlight clinical trial designs, biologic issues, and regulatory issues leading to the development of medications for tissue-agnostic treatment.