Expert Review of Precision Medicine and Drug Development最新文献

{"title":"The future of precision medicine in oncology","authors":"Ahmad Z. Al Meslamani","doi":"10.1080/23808993.2023.2292988","DOIUrl":"https://doi.org/10.1080/23808993.2023.2292988","url":null,"abstract":"","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"73 10","pages":"43 - 47"},"PeriodicalIF":1.2,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide receptor radionuclide therapy in neuroendocrine neoplasms and related tumors: from fundamentals to personalization and the newer experimental approaches","authors":"Sarvesh Loharkar, S. Basu","doi":"10.1080/23808993.2023.2211090","DOIUrl":"https://doi.org/10.1080/23808993.2023.2211090","url":null,"abstract":"","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"1 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48352759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying patients suitable for targeted adjuvant therapy: advances in the field of developing biomarkers for tumor recurrence following irradiation.","authors":"S Jagasia, E Tasci, Ying Zhuge, K Camphausen, A V Krauze","doi":"10.1080/23808993.2023.2276927","DOIUrl":"10.1080/23808993.2023.2276927","url":null,"abstract":"<p><strong>Introduction: </strong>Radiation therapy (RT) is commonly used to treat cancer in conjunction with chemotherapy, immunotherapy, and targeted therapies. Despite the effectiveness of RT, tumor recurrence due to treatment resistance still lead to treatment failure. RT-specific biomarkers are currently lacking and remain challenging to investigate with existing data since, for many common malignancies, standard of care (SOC) paradigms involve the administration of RT in conjunction with other agents.</p><p><strong>Areas covered: </strong>Established clinically relevant biomarkers are used in surveillance, as prognostic indicators, and sometimes for treatment planning; however, the inability to intercept early recurrence or predict upfront resistance to treatment remains a significant challenge that limits the selection of patients for adjuvant therapy. We discuss attempts at intercepting early failure. We examine biomarkers that have made it into the clinic where they are used for treatment monitoring and management alteration, and novel biomarkers that lead the field with targeted adjuvant therapy seeking to harness these.</p><p><strong>Expert opinion: </strong>Given the growth of data correlating interventions with omic analysis toward identifying biomarkers of radiation resistance, more robust markers of recurrence that link to biology will increasingly be leveraged toward targeted adjuvant therapy to make a successful transition to the clinic in the coming years.</p>","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"8 1","pages":"33-42"},"PeriodicalIF":1.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of drug combinations for lung cancer patients whose tumors are unresponsive to targeted therapy: clinical bases and future directions","authors":"D. Rocco, L. Della Gravara, P. Maione, G. Palazzolo, C. Gridelli","doi":"10.1080/23808993.2022.2050369","DOIUrl":"https://doi.org/10.1080/23808993.2022.2050369","url":null,"abstract":"ABSTRACT Introduction Targeted therapies have granted unprecedented results in terms of survival and safety to oncogene-addicted advanced NSCLC patients. However, these patients eventually become unresponsive to such treatments due to several different resistance mechanisms. Moreover, the current lack of subsequent-line treatments forces these patients to receive less tolerable and less effective chemotherapy regimens. Areas covered Thus, this paper aims to review the current state of the art with respect to targeted therapies for the treatment of oncogene-addicted advanced NSCLC patients, focusing on resistance mechanisms and on drug combinations to overcome them. Expert opinion We strongly believe that a personalized sequential treatment approach based on resistance mutations will become the standard of care for oncogene-addicted advance NSCLC patients. Furthermore, we believe that TKI combination regimens will play a key role. In the same vein, ICI-containing regimens will play a part both in patients without druggable resistance mutations and in patients progressing on TKI therapies.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"29 - 38"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60122089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-L1 assessment in breast cancer immunotherapy: a critical overview","authors":"A. Ricci, Alessandro Rizzo, G. Palmiotti, G. Brandi","doi":"10.1080/23808993.2022.2094766","DOIUrl":"https://doi.org/10.1080/23808993.2022.2094766","url":null,"abstract":"The advent of immune checkpoint inhibitors (ICIs) has recently made a breakthrough in several hematological and solid tumors including, among others, non-small-cell lung cancer, renal cell carcinoma, melanoma, urothelial carcinoma, and hepatocellular carcinoma [1–3]. These agents are able to enhance antitumor activity, leading to an increase in the cytotoxicity of T cells and the blocking of downregulators of immunity such as programmed cell death protein 1 (PD-1) and its ligand PD-L1, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and lymphocyte activating-3 (LAG-3) [4]. ICIs have also been recently assessed in breast cancer (BC), as monotherapy or in combination with other anticancer agents. First, monotherapy with ICIs has reported disappointing results in unselected triple-negative BC (TNBC), with approximately one-quarter of patients achieving response [5]; in fact, the KEYNOTE-086 and the KEYNOTE-119 trials evaluating pembrolizumab monotherapy highlighted response rates lower than 10%, and these findings have also been confirmed by clinical studies evaluating other immunotherapies, such as single-agent atezolizumab [6]. Thus, several combination treatments have been investigated, based on the synergistic effect of ICIs plus other anticancer agents with different mechanism of action. Among these combinatorial strategies, and following the results of landmark trials, chemoimmunotherapy has entered into clinical practice as new front-line treatment in TNBC patients with metastatic disease and PD-L1 overexpression or elevated combined positive score (CPS) [7]. Moreover, a large number of phase I to III clinical trials are assessing immunebased combinations, with these studies having the potential to further shape the direction of firstand later-line therapy in this patient population. However, a high unmet need in BC immunotherapy remains the lack of biomarkers predictive of response to ICIs. In fact, if PD-L1 is considered the most reliable predictor, its assessment presents several limitations, and it is far from being standardized [8]. The expression of PD-L1 is typically detected on tumor cells (TC) or immune cells (IC), and in recent years, PD-L1 assessment has emerged as an important predictive biomarker of response to immunotherapy in several tumor types (e.g. nonsmall-cell lung cancer, head and neck cancer, and gastric cancer) [9,10]. As regards BC, PD-L1 status has been associated with a prognostic value, and high PD-L1 expression seems to predict worse clinical outcomes in triple-negative BC patients [11]. PD-L1 has been validated as a predictor of response to chemoimmunotherapy in metastatic BC and has entered into everyday clinical practice, following the results of recently published IMpassion130 and KEYNOTE-355 phase III clinical trials [12,13]. The IMpassion130 compared chemoimmunotherapy with atezolizumab–nab-paclitaxel versus placebo plus nabpaclitaxel as front-line treatment in TNBC patients with metastatic disease [12]; the copri","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"58 - 59"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44040888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiding treatment selection with immunotherapy compared to targeted therapy agents in patients with metastatic kidney cancer","authors":"M. Rosellini, Andrea Marchetti, Elisa Tassinari, Giacomo Nuvola, Alessandro Rizzo, M. Santoni, V. Mollica, F. Massari","doi":"10.1080/23808993.2022.2156786","DOIUrl":"https://doi.org/10.1080/23808993.2022.2156786","url":null,"abstract":"ABSTRACT Introduction Kidney cancer treatment has been first revolutionized by the advent of targeted therapies (TKIs and mTOR inhibitors) and then by the approval of immunotherapy and immunocombinations. Whereas immunocombinations represent the most used first-line therapy in intermediate/poor risk patients with clear-cell tumors, cabozantinib and nivolumab are both effective compounds at progression, and till today it is not totally clear what to prefer. No standard treatments are approved in post-second-line setting and in non-clear carcinoma. Areas covered The aim of this review is to summarize the main evidence supporting the use of targeted therapies and immunotherapy, in every setting of clear-cell and non-clear cell renal cell carcinoma, while also providing an insight into promising ongoing and upcoming trials. Expert opinion We speculate on what could help physicians in guiding the therapeutic decision-making process in advanced kidney cancer. International mRCC Database Consortium criteria are still recommended for the choice of primary treatments, despite presenting several limitations in the current immunotherapy-era. Multiple predictors of response to immunotherapy or targeted therapies are emerging but validated biomarkers are awaited. Furthermore, we discuss therapeutic sequences in kidney cancer, guessing how physicians may prefer immunotherapy or TKI as later-line strategies on the basis of previous treatments. Summary The therapeutic armamentarium for advanced clear cell RCC has been revolutionized by the approval of novel immune-based combinations in the last decade. Anti-VEGF TKI as a first-line treatment still represents a valid choice in good risk patients or in subjects who are not able to receive immunocombinations. Several compounds are available in second-line after TKI monotherapy, but no specific indications are available after immunocombinations. Cabozantinib seems to be the option with the strongest rationale and the most widely investigated, but the issue is still open. No standard therapy is approved for non-clear cell patients, although cabozantinib is emerging as the most promising option. Data regarding immunotherapy are still awaited. Prospective and molecular-driven trials enrolling non-clear patients are required. No predictive biomarkers have been validated to guide physician’s treatment choice, toward TKIs or either immunotherapic compounds. Future efforts are necessary to improve the predictive role of novel emerging biomarkers in both clear cell and non-clear cell histologies, such as gene expression profiling and tumor microenvironment features.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"131 - 149"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44241389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of GABAA receptor subunit expression abnormalities in fragile X syndrome","authors":"Mathijs B. van der Lei, R. Kooy","doi":"10.1080/23808993.2021.2008168","DOIUrl":"https://doi.org/10.1080/23808993.2021.2008168","url":null,"abstract":"ABSTRACT Introduction Many studies have reported brain region and age-dependent alterations in the expression of several subunits of the GABAA receptor in Fmr1 KO mice. GABAA receptors are located synaptic and extrasynaptic with differential subunit compositions and characteristics. Interestingly, the activity of many subunits of the GABAA receptor is amendable by differential pharmacological treatment. Areas Covered The purpose of this review is to summarize the expression of GABAA receptor subunits in different brain regions of Fmr1 KO mice across different ages. The decreased expression of the synaptic α2 subunit in juvenile, and the decreased expression of the extrasynaptic δ subunit in both juvenile and adult Fmr1 KO mice, are among the most consistent abnormalities reported. Both subunits are suitable for treatment and currently available compounds are discussed in this review along with their therapeutic potential. Expert Opinion Pharmacological treatment targeting specific subunits of the GABAA receptor has shown selective improvements in fragile X syndrome. To our knowledge, combinatorial therapies targeting multiple subunits of the GABAA receptor have not been explored. We here argue that such a combination therapy could induce a synergistic effect to ameliorate the clinical symptoms of fragile X syndrome.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"105 - 120"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42488143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of response for hepatocellular carcinoma immunotherapy: is there anything on the horizon?","authors":"Alessandro Rizzo, A. Ricci","doi":"10.1080/23808993.2022.2075724","DOIUrl":"https://doi.org/10.1080/23808993.2022.2075724","url":null,"abstract":"ABSTRACT Introduction Hepatocellular carcinoma (HCC) remains an important cause of cancer-related death, representing the sixth most commonly diagnosed malignancy worldwide. Novel systemic treatment options have recently emerged for advanced diseases, including immune checkpoint inhibitors (ICIs), as monotherapy or in combination with other anticancer agents. However, several questions remain unanswered, including the identification of predictors of response to immunotherapy in this setting. Areas Covered Herein, we will provide a critical overview of current knowledge regarding predictive biomarkers of response to ICIs in HCC patients. A literature search was conducted in December 2021 of PubMed/Medline, Cochrane library, and Scopus databases. Expert Opinion Several critical issues regarding the role of ICIs in advanced HCC remain unsolved, with the identification of predictive biomarkers representing an unmet need. Further efforts aimed at identifying reliable predictors and the effective role of PD-L1 status, TMB, MSI, and other biomarkers are warranted.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"50 - 57"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42272331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction and early diagnosis of immune-checkpoint inhibitor-induced inflammatory arthritis from molecular biomarkers – Where are we now?","authors":"Christopher Aboo, Tue Wenzel Krastrup, H. Tenstad, Jie Ren, S. A. Just, M. Ladekarl, A. Stensballe","doi":"10.1080/23808993.2022.2156785","DOIUrl":"https://doi.org/10.1080/23808993.2022.2156785","url":null,"abstract":"ABSTRACT Introduction Immune-checkpoint inhibitors (ICI) works by blocking inhibitory signals of T cells. This produces an effective anti-tumor response but can also cause immune-related adverse events (irAEs). Most irAEs are transient, but ICI-induced inflammatory arthritis (ICI-IIA) might become chronic and affect the quality-of-life, or even necessitate treatment discontinuation. However, there exist no tools to identify patients that are susceptible to develop ICI-IIA. Areas covered This non-systematic review briefly presents a sparse number of studies, that have tried to identify circulating biomarkers for early prediction of ICI-IIA. Challenges, recommendations, and possibilities related to biomarker discovery in the context of ICI-IIA are then covered. Expert opinion Improved diagnosis adapted from rheumatological settings is needed for future studies to avoid a major pitfall of bad endpoints. Synovial tissue biopsies, omics technologies and particularly integration of multiple omics data is useful when searching for biomarkers of ICI-IIA and can also help unravel underlying biological mechanisms. Future biomarkers could ultimately aid clinical decision-making and facilitate early prophylaxis, pave the way for new treatment or even translational models to study autoimmune arthritis.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"162 - 168"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45829306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating precision ophthalmology: recent advances","authors":"Loay Rahman, Ammaarah Hafejee, Rajeevan Anantharanjit, Wei Wei, M. Cordeiro","doi":"10.1080/23808993.2022.2154146","DOIUrl":"https://doi.org/10.1080/23808993.2022.2154146","url":null,"abstract":"ABSTRACT Introduction The future of ophthalmology is precision medicine. With a growing incidence of lifestyle-associated ophthalmic disease such as diabetic retinopathy, the use of technology has the potential to overcome the burden on clinical specialists. Advances in precision medicine will help improve diagnosis and better triage those with higher clinical need to the appropriate experts, as well as providing a more tailored approach to treatment that could help transform patient management. Areas covered A detailed literature review was conducted using OVID Medline and PubMed databases to explore advances in precision medicine within the areas of retinal disease, glaucoma, cornea, cataracts and uveitis. Over the last three years [2019 – 2022] are explored, particularly discussing technological and genomic advances in screening, diagnosis, and management within these fields. Expert opinion Artificial intelligence and its subspecialty deep learning provide the most substantial ways in which diagnosis and management of ocular diseases can be further developed within the advancing field of precision medicine. Future challenges include optimal training sets for algorithms and further developing pharmacogenetics in more specialized areas.","PeriodicalId":12124,"journal":{"name":"Expert Review of Precision Medicine and Drug Development","volume":"7 1","pages":"150 - 161"},"PeriodicalIF":1.2,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46231060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}