Project description:Precision radiotherapy, which accurately delivers the dose on a tumor and confers little or no irradiation to the surrounding normal tissue and organs, results in maximum tumor control and decreases the toxicity to the utmost extent. Proton beam therapy (PBT) provides superior dose distributions and has a dosimetric advantage over photon beam therapy. Initially, the clinical practice and study of proton beam therapy focused on ocular tumor, skull base, paraspinal tumors (chondrosarcoma and chordoma), and unresectable sarcomas, which responded poorly when treated with photon radiotherapy. Then, it is widely regarded as an ideal mode for reirradiation and pediatrics due to reducing unwanted side effects by lessening the dose to normal tissue. During the past decade, the application of PBT has been rapidly increasing worldwide and gradually expanding for the treatment of various malignancies. However, to date, the role of PBT in clinical settings is still controversial, and there are considerable challenges in its application. We systematically review the latest advances of PBT and the challenges for patient treatment in the era of precision medicine.
Project description:Migraine is a common neurovascular disorder in the neurologic clinics whose mechanisms have been explored for several years. The aura has been considered to be attributed to cortical spreading depression (CSD) and dysfunction of the trigeminovascular system is the key factor that has been considered in the pathogenesis of migraine pain. Moreover, three genes (CACNA1A, ATP1A2, and SCN1A) have come from studies performed in individuals with familial hemiplegic migraine (FHM), a monogenic form of migraine with aura. Therapies targeting on the neuropeptids and genes may be helpful in the precision medicine of migraineurs. 5-hydroxytryptamine (5-HT) receptor agonists and calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated efficacy in the acute specific treatment of migraine attacks. Therefore, ongoing and future efforts to find new vulnerabilities of migraine, unravel the complexity of drug therapy, and perform biomarker-driven clinical trials are necessary to improve outcomes for patients with migraine.
Project description:The past decade has been transformative for lung cancer patients, physicians, and scientists. The discovery of EGFR mutations that confer sensitivity to tyrosine kinase inhibitors in lung adenocarcinomas in 2004 heralded the beginning of the era of precision medicine for lung cancer. Indeed, it precipitated concerted efforts by many investigators to define molecular subgroups of lung cancer, characterize the genomic landscape of lung cancer subtypes, identify novel therapeutic targets, and define mechanisms of sensitivity and resistance to targeted therapies. The fruits of these efforts are visible every day now in lung cancer clinics: Patients receive molecular testing to determine whether their tumor harbors an actionable mutation, new and improved targeted therapies that can overcome resistance to first-generation drugs are in clinical trials, and drugs targeting the immune system are showing activity in patients. This extraordinary promise is tempered by the sobering fact that even the newest treatments for metastatic disease are rarely curative and are effective only in a small fraction of all patients. Ongoing and future efforts to find new vulnerabilities of lung cancers, unravel the complexity of drug resistance, increase the efficacy of immunotherapies, and perform biomarker-driven clinical trials are necessary to improve outcomes for patients with lung cancer.
Project description:Prostate cancer is the second most common male cancer affecting Western society. Despite substantial advances in the exploration of prostate cancer biomarkers and treatment strategies, men are over diagnosed with inert prostate cancer, while there is also a substantial mortality from the invasive disease. Precision medicine is the management of treatment profiles across different cancers predicting therapies for individual cancer patients. With strategies including individual genomic profiling and targeting specific cancer pathways, precision medicine for prostate cancer has the potential to impose changes in clinical practices. Some of the recent advances in prostate cancer precision medicine comprise targeting gene fusions, genome editing tools, non-coding RNA biomarkers, and the promise of liquid tumor profiling. In this review, we will discuss these recent scientific advances to scale up these approaches and endeavors to overcome clinical barriers for prostate cancer precision medicine.
Project description:Gastric cancer (GC) remains the third most common cause of cancer death worldwide, with limited therapeutic strategies available. With the advent of next-generation sequencing and new preclinical model technologies, our understanding of its pathogenesis and molecular alterations continues to be revolutionized. Recently, the genomic landscape of GC has been delineated. Molecular characterization and novel therapeutic targets of each molecular subtype have been identified. At the same time, patient-derived tumor xenografts and organoids now comprise effective tools for genetic evolution studies, biomarker identification, drug screening, and preclinical evaluation of personalized medicine strategies for GC patients. These advances are making it feasible to integrate clinical, genome-based and phenotype-based diagnostic and therapeutic methods and apply them to individual GC patients in the era of precision medicine.
Project description:For the past three decades, the use of genomics to inform drug discovery and development pipelines has generated both excitement and scepticism. Although earlier efforts successfully identified some new drug targets, the overall clinical efficacy of developed drugs has remained unimpressive, owing in large part to the heterogeneous causes of disease. Recent technological and analytical advances in genomics, however, have now made it possible to rapidly identify and interpret the genetic variation underlying a single patient's disease, thereby providing a window into patient-specific mechanisms that cause or contribute to disease, which could ultimately enable the 'precise' targeting of these mechanisms. Here, we first examine and highlight the successes and limitations of the earlier phases of genomics in drug discovery and development. We then review the current major efforts in precision medicine and discuss the potential broader utility of mechanistically guided treatments going forward.
Project description:First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such as fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), BRAF, human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI)-high, neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), and poly (adenosine diphosphate-ribose) polymerase (PARP). This review summarizes currently available options in precision medicine and clinical trials for patients with advanced BTC.
Project description:Rapid methodological advances in statistical and computational genomics have enabled researchers to better identify and interpret both rare and common variants responsible for complex human diseases. As we continue to see an expansion of these advances in the field, it is now imperative for researchers to understand the resources and methodologies available for various data types and study designs. In this review, we provide an overview of recent methods for identifying rare and common variants and understanding their roles in disease etiology. Additionally, we discuss the strategy, challenge, and promise of gene therapy. As computational and statistical approaches continue to improve, we will have an opportunity to translate human genetic findings into personalized health care.
Project description:Recent advances in technology and better understanding of mechanisms underlying disease are beginning to enable us to better characterize critically ill patients. Instead of using nonspecific syndromic groupings, such as sepsis or acute respiratory distress syndrome, we can now classify individual patients according to various specific characteristics, such as immune status. This "personalized" medicine approach will enable us to distinguish patients who have similar clinical presentations but different cellular and molecular responses that will influence their need for and responses (both negative and positive) to specific treatments. Treatments will be able to be chosen more accurately for each patient, resulting in more rapid institution of appropriate, effective therapy. We will also increasingly be able to conduct trials in groups of patients specifically selected as being most likely to respond to the intervention in question. This has already begun with, for example, some new interventions being tested only in patients with coagulopathy or immunosuppressive patterns. Ultimately, as we embrace this era of precision medicine, we may be able to offer precision therapies specifically designed to target the molecular set-up of an individual patient, as has begun to be done in cancer therapeutics.