Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types.This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required.While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.
- Keywords
- genomics, metronomic chemotherapy, precision medicine, targeted therapy,
- MeSH
- Child MeSH
- Precision Medicine * MeSH
- Clinical Trials as Topic MeSH
- Medical Oncology * MeSH
- Humans MeSH
- Neoplasms drug therapy genetics MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Research Design MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Review MeSH
The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth.
- Keywords
- Spatially Fractionated Radiation Therapy, immunotherapy, in-silico model, mathematical framework, radiotherapy,
- Publication type
- Journal Article MeSH
During the past 20 years, targeted therapy based on the understanding of tumor biology has been complementing or even replacing cytotoxic agents that have dominated pharmacotherapy of cancer since the conception of medical oncology. Unfortunately, the fact that targeted therapies with potential to induce cure or at least substantially prolong survival are still not available for many common solid tumors results in skepticism or even nihilism. On the one hand, biomarker research is not keeping pace with the introduction of new agents, while on the other hand, effective drugs are still not available for many potential molecular targets associated with malignant transformation and tumor progression. However, targeted therapies have already transformed the natural history and clinical outcomes not only in patients with rare malignancies like gastrointestinal stromal tumor but also with many common tumors, e.g. breast cancer, malignant melanoma, non-small cell lung cancer or renal cell carcinoma. For further advances, a multidisciplinary effort is indispensible that should, above all, involve the collaboration of medical oncology and laboratory medicine.
- Keywords
- biomarkers, cancer, immunotherapy, targeted therapy,
- MeSH
- Antineoplastic Agents therapeutic use MeSH
- Molecular Targeted Therapy * MeSH
- Precision Medicine trends MeSH
- Humans MeSH
- Biomarkers, Tumor * MeSH
- Neoplasms therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antineoplastic Agents MeSH
- Biomarkers, Tumor * MeSH
Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period.
- Keywords
- DNA sequencing, Urachal carcinoma, carcinoembryonic antigen (CEA), chemotherapy, drug screening, immune checkpoint inhibitor (ICI) therapy, targeted therapy,
- MeSH
- Adult MeSH
- Precision Medicine * methods MeSH
- Humans MeSH
- Urinary Bladder Neoplasms * genetics diagnosis drug therapy pathology MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
PURPOSE OF REVIEW: To provide an update on the implementation of precision medicine, based on treatable traits and mechanisms, in the daily clinical management of chronic airways diseases. RECENT FINDINGS: Recent insights into the complex and heterogeneous nature of chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma identified several clinical and inflammatory phenotypes. This shifted the management focus of these diseases away from the prototypic disease labels and paved the way for developing novel targeted therapies.The concept of precision medicine aims to link the right patient to the right treatment, while minimizing the risk of adverse effects. Several treatable features ('treatable traits') have now been identified for these chronic airway diseases, including pulmonary, extra-pulmonary, and psychological/lifestyle/environmental traits. As the next step, innovative detection techniques should clarify underlying mechanisms and molecular pathways of these treatable traits and novel reliable point-of-care (composite) biomarkers to help predict responders to targeted therapies must be developed. SUMMARY: Precision medicine links the right patient to the right treatment. Identification of treatable traits in asthma and COPD will help optimize the treatment approach in these heterogeneous diseases. Furthermore, in-depth identification of underlying molecular pathways and reliable biomarkers in chronic airways diseases to guide targeted treatment in individual patients is in progress.
PURPOSE OF REVIEW: Bladder cancer incidence is on the rise, and until recently, there has been little to no change in treatment regimens over the last 40 years. Hence, it is imperative to work on strategies and approaches to untangle the complexity of intra- and inter-tumour heterogeneity of bladder cancer with the aim of improving patient-specific care and treatment outcomes. The focus of this review is therefore to highlight novel targets, advances, and therapy approaches for bladder cancer patients. RECENT FINDINGS: The success of combining an antibody-drug conjugate (ADC) with immunotherapy has been recently hailed as a game changer in treating bladder cancer patients. Hence, interest in other ADCs as a treatment option is also rife. Furthermore, strategies to overcome chemoresistance to standard therapy have been described recently. In addition, other studies showed that targeting genomic alterations (e.g. mutations in FGFR3 , DNA damage repair genes and loss of the Y chromosome) could also be helpful as prognostic and treatment stratification biomarkers. The use of single-cell RNA sequencing approaches has allowed better characterisation of the tumour microenvironment and subsequent identification of novel targets. Functional precision medicine could be another avenue to improve and guide personalized treatment options. SUMMARY: Several novel preclinical targets and treatment options have been described recently. The validation of these advances will lead to the development and implementation of robust personalized treatment regimens for bladder cancer patients.
- MeSH
- Molecular Targeted Therapy methods MeSH
- Immunoconjugates therapeutic use MeSH
- Immunotherapy methods MeSH
- Precision Medicine * methods MeSH
- Humans MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Tumor Microenvironment drug effects MeSH
- Urinary Bladder Neoplasms * genetics therapy drug therapy pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Immunoconjugates MeSH
- Biomarkers, Tumor MeSH
The precision medicine (PM) initiative is a response to the dismal outlook in solid cancer. Despite heterogeneity, common mechanistic denominators may exist across the spectrum of solid cancer. A shift from conventional research and development (R&D) toward PM will require conceptual and structural change. As individuals and as a society, we welcome innovation, but question change. We ask: In solid cancer, does PM identify and address the causes of prior failures, and, if so, are the proposed solutions feasible? And, when may we expect safer, more effective and affordable drugs in the clinic? Considerations that prompt a pragmatic rethink include a failure analysis of translational R&D in solid cancer suggesting that trials and regulations need to be aligned with the natural history of the disease. In successful therapeutic interventions in chronic, complex disease, surrogate markers and endpoints should be consistent with the Prentice's criteria. In solid cancer, drug induced tumor shrinkage, is a drug effect and not a disease response; tumor shrinkage does not reflect nor predict interruption of the disease. Overall, we support a pragmatic, multidisciplinary, and collaborative R&D, and suggest that direction be set by clinical need and utility, and by questions, not answers. PM will prove worthwhile if it could improve clinical outcomes. The lag in therapeutics relative to diagnostics is a cause for confusion. Overdiagnosis adds to fear and harm, especially in the absence of effective interventions. A revised initiative that prioritizes metastasis research could replicate the successful HIV/AIDS model in solid cancer. A pragmatic approach may further translational efforts toward meaningfully effective, generally available, and affordable solutions.
- Keywords
- 21st Century Cures Act, Paul Ehrlich, RECIST, metastasis, pragmatism, precision medicine, solid cancer, translation,
- Publication type
- Journal Article MeSH
Historically the treatment of lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody (ANCA) vasculitis was 'one size fits all'; however, with the emergence of precision medicine initiatives, the field is moving towards more personalized treatment approaches. The recent development of a more accurate and reproducible histopathological classification system for LN could lead to better disease categorization and therefore more targeted therapies. A better understanding of the pathophysiology of LN has provided evidence that not only T but also B cells play an important role, opening new opportunities for individualized treatment approaches. Recent trials have shown calcineurin inhibitors and the anti-CD20 antibodies rituximab and ofatumumab to be effective in the treatment of LN, adding new treatment options. State-of-the-art targeted therapy in ANCA-associated vasculitis (AAV) takes interindividual heterogeneity in disease severity, type of ANCA antibody [myeloperoxidase versus proteinase 3 (PR3)] and the risk for side effects of therapy into consideration. In addition, within an individual, induction therapy differs from maintenance therapy, the same holding true in incident and relapsing disease. Rituximab is now widely used in AAV and it has become clear that prolonged B cell depletion, as in LN, must be achieved to obtain a long-lasting clinical response, especially in anti-PR3-associated disease. Still, despite these advances, molecular and genetic markers are rarely incorporated into diagnostic and treatment algorithms and true precision medicine remains an aspiration that hopefully can be achieved.
- Keywords
- ANCA, calcineurin inhibitors, lupus nephritis, rituximab, vasculitis,
- MeSH
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * drug therapy MeSH
- Precision Medicine MeSH
- Humans MeSH
- Myeloblastin MeSH
- Lupus Nephritis * diagnosis drug therapy etiology MeSH
- Antibodies, Antineutrophil Cytoplasmic MeSH
- Rituximab therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Myeloblastin MeSH
- Antibodies, Antineutrophil Cytoplasmic MeSH
- Rituximab MeSH
INTRODUCTION: Central and Eastern European Proteomic Conference (CEEPC) provides a platform for researchers to discuss multi-disciplinary integrated approaches to address a range of challenges from present day viral pandemic to on-going progress in Precision Medicine. CEEPC brings together various multi-omics entwined with novel enabling technologies, thus facilitating conceptual advances from cell to society for the benefit of mankind. AREAS COVERED: Proteomic methodologies, databases and software has revolutionized our ability to assess protein interactions and cellular changes, allowing the establishment of biological connections and identification of important cellular regulatory proteins and pathways previously unknown or not fully understood. Additionally, Mass spectrometry (MS) remains a major driving force in the field of 'multi-omics' and a powerful technology for the structural characterization of biomolecules and for analysis of proteins and small molecules such as lipids, sugars and metabolites. Combination of measurements from proteomics, genomics, epigenomics, transcriptomics and metabolomics, present a powerful decision-making format allowing deeper interpretation of a disease scenario in Precision medicine. EXPERT COMMENTARY: Precision Medicine offers novel and promising ways to identify and treat a wide range of diseases. The future success of these therapies will be underpinned by novel proteo-genomic approaches linked to sophisticated databases to evaluate and predict drug-patient interactions.
- Keywords
- Biomarkers, cancer, clinical proteomics, exosomes, mass Spectrometry Imaging, multi-proteomics, precision medicine, socio-humanitarian, systems Biology, viral proteomics,
- MeSH
- Genomics trends MeSH
- Precision Medicine trends MeSH
- Humans MeSH
- Metabolomics trends MeSH
- Proteomics trends MeSH
- Software MeSH
- Computational Biology trends MeSH
- Check Tag
- Humans MeSH
- Publication type
- Congress MeSH
- Geographicals
- Poland MeSH
- Keywords
- clinical trial designs, drug models, pediatric oncology, personalized medicine, personalized precision pediatric oncology, precision oncology, trial models,
- Publication type
- Editorial MeSH
