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Simple Summary: This research is the first comprehensive study in New Zealand to categorise and examine the characteristics of breast cancer based on HER2 status. We explored three HER2 categories: HER2-zero, HER2-low, and HER2-positive, in women diagnosed with invasive breast cancer. Utilising Te Rēhita Mate Ūtaetae (Breast Cancer Foundation NZ National Register), our study analysed data spanning 21 years, revealing that most women underwent HER2 testing. Significantly, many cases previously not recognised as having significant HER2 levels were in fact HER2-low, qualifying them for newer, targeted drug therapies. These findings are particularly crucial as they suggest that newer therapies could benefit a larger segment of patients, notably those with advanced breast cancer; approximately 60% of these women might now benefit from these innovative HER2-targeted treatments. The study underscores the urgent need for standardised HER2 testing to personalise and optimise treatment, enhancing outcomes for patients with invasive breast cancer. Objectives: To perform the first national analysis of demographic and clinicopathological features associated with the HER2 positive, HER2-low, and HER2-zero invasive breast cancers in New Zealand. The study will reveal the proportion of women who may benefit from new HER2-targeted antibody drug conjugate (ADC) therapies. Methods: Utilising data from Te Rēhita Mate Ūtaetae (Breast Cancer Foundation NZ National Register), the study analysed data from women diagnosed with invasive breast cancer over a 21-year period. The HER2 status of tumours was classified into three categories—HER2-zero, HER2-low, HER2-positive. Results: From 2009–2021, 94% of women underwent HER2 testing, with 14% diagnosed with HER2-positive breast cancer. For advanced-stage disease, 38% of those formerly classified as HER2-negative were reclassified as HER2-low. Including HER2-positive breast cancers, this indicates that 60% of women with advanced breast cancer may potentially benefit from the new HER2-directed ADCs (approximately 120 women per year). Conclusions: The findings suggest a significant proportion of women with invasive breast cancer in New Zealand could benefit from new HER2-targeted treatments. There is a need to standardise HER2 testing to enhance personalised treatment and improve outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment with targeted agents is an emerging concept for cholangiocarcinoma, a rare cancer with a lack of effective therapies. However, there is limited real-world evidence regarding the use of targeted agents using molecular profiling data from liquid biopsies in clinical practice. This single-centre retrospective study aimed to characterise treatment efficacy and predictors of clinical benefit in cholangiocarcinoma following targeted therapies. Our findings suggest that patients with exposure to targeted agents and response to such treatment are the greatest beneficiaries of this personalized treatment approach; those with previous localised approaches such as surgery had further benefit, suggesting that localised treatment options can be considered in appropriate cases. Further research is needed to identify patients who are most likely to benefit from targeted agents using the liquid biopsy approach and evaluate the optimal sequence of such therapies to maximise treatment response and survival outcomes in this challenging clinical population. Background: Cholangiocarcinoma (CCA) is associated with poor outcomes and limited treatment options, leading to increased use of targeted therapies for its management. Here, we performed one of the largest single-centre reviews evaluating outcomes following personalised targeted agents in CCA patients. Methods: All consecutive CCA patients receiving systemic therapy between January 2010 and April 2023 at UCLH were included. The primary objective of this study was to evaluate treatment response, survival outcomes and predictors of clinical benefit in CCA patients treated with molecularly guided therapies. Patient demographic factors, disease characteristics and survival outcomes were evaluated using the Kaplan–Meier method and Cox proportional-hazards models. Results: Of the 227 consecutive CCA patients, 162 (71%) had molecular profiling, of whom 56 (35%) were eligible and 55 received molecular-targeted treatment. CCA histological classifications comprised intrahepatic (N = 32), extrahepatic (N = 11), hilar (N = 4) and unknown (N = 9) subtypes. Most patients received targeted agents based on genomic profiling in a second treatment line setting (N = 34). Frequently observed genomic alterations occurred in the FGFR2 (N = 21), IDH1 (N = 7) and BRCA2 (N = 6) genes. Median progression-free survival (PFS) following first-, second- and third-line systemic therapy and overall survival (OS) were 8.44 (95% CI, 7.49–12.78), 5.65 (95% CI, 3.71–7.13), 5.55 (2.79–12.58) and 29.01 (24.21–42.91) months, respectively. CCA subtype and FGFR/BRCA molecular aberration status were not associated with PFS or OS. However, a prior CCA-related surgical history was predictive of OS (p = 0.02). Stratification by best overall response to second-line targeted agents demonstrated an association with PFS (p = 0.002) and OS (p = 0.02). Duration of treatment with second-line targeted therapy was associated with OS (p < 0.001). Conclusions: Patients receiving targeted therapeutics achieved promising outcomes, especially those attaining a favourable treatment response and those receiving targeted agents for longer periods. Liquid biopsies can reliably provide information on extended molecular profiling to aid patient selection for personalised therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Many anti-cancer drugs are prescribed at a 'one-size fits all' starting dose, without considering individual differences. This is a problem for many cancer patients as this fixed dose might be too much for an individual which could lead to adverse effects and toxicity. Similarly, the fixed-dose might not be enough for some patients which could lead to therapeutic failure. Achieving the right amount of anti-cancer drugs in the body is critical, however, currently, the anti-cancer drug concentrations are not monitored in routine care. Our group used our extensive experience, existing published frameworks and recommendations to establish our own framework to implement a program that enables individualized dosing of anti-cancer drugs in routine care. This paper describes this framework with a simple 6-step process that can be utilised for the implementation of individualised dosing programs for anti-cancer drugs. Precision medicine in oncology involves identifying the 'right drug', at the 'right dose', for the right person. Currently, many orally administered anti-cancer drugs, particularly kinase inhibitors (KIs), are prescribed at a standard fixed dose. Identifying the right dose remains one of the biggest challenges to optimal patient care. Recently the Precision Dosing Group established the Accurate Dosing of Anti-cancer Patient-centred Therapies (ADAPT) Program to address individualised dosing; thus, use existing anti-cancer drugs more safely and efficiently. In this paper, we outline our framework, based on the Medical Research Council (MRC) framework, with a simple 6-step process and strategies which have led to the successful implementation of the ADAPT program in South Australia. Implementation strategies in our 6-step process involve: (1) Evaluate the evidence and identify the cancer drugs: Literature review, shadowing other experts, establishing academic partnerships, adaptability/flexibility; (2) Establishment of analytical equipment for drug assays for clinical purposes: assessment for readiness, accreditation, feasibility, obtaining formal commitments, quality assurance to all stakeholders; (3) Clinical preparation and education: educational material, conducted educational meetings, involve opinion leaders, use of mass media, promote network weaving, conduct ongoing training; (4) Blood collection, sample preparation and analyses: goods received procedures, critical control points (transport time); (5) Interpret and release results with recommendations: facilitate the relay of clinical data to providers; (6) Clinical application: providing ongoing consultation, identify early adopters, identify, and prepare champions. These strategies were selected from the 73 implementation strategies outlined in the Expert Recommendations for Implementing Change (ERIC) study. The ADAPT program currently provides routine plasma concentrations for patients on several orally administered drugs in South Australia and is currently in its evaluation phase soon to be published. Our newly established framework could provide great potential and opportunities to advance individualised dosing of oral anti-cancer drugs in routine clinical care. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is among the most prevalent cancers for men globally, accounting for 13% of cancer diagnoses in the male population each year. Surgical intervention is the primary treatment option but fails in up to 40% of patients, who experience biochemical recurrence (BCR). Determining the likelihood of recurrence and the length of time between surgery and BCR is critical for patient treatment decision-making. Traditional predictive models exploit routine clinical variables such as cancer stage, and may be improved upon by leveraging other accessible information about the patient. This study considers including patient-specific genomic data to identify relevant additional predictors of BCR-free survival, which requires the use of modern machine learning techniques. The results of this study indicate that including such genomic data leads to a gain in BCR prediction performance over models using clinical variables only. Predicting the risk of, and time to biochemical recurrence (BCR) in prostate cancer patients post-operatively is critical in patient treatment decision pathways following surgical intervention. This study aimed to investigate the predictive potential of mRNA information to improve upon reference nomograms and clinical-only models, using a dataset of 187 patients that includes over 20,000 features. Several machine learning methodologies were implemented for the analysis of censored patient follow-up information with such high-dimensional genomic data. Our findings demonstrated the potential of inclusion of mRNA information for BCR-free survival prediction. A random survival forest pipeline was found to achieve high predictive performance with respect to discrimination, calibration, and net benefit. Two mRNA variables, namely ESM1 and DHAH8, were identified as consistently strong predictors with this dataset. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is the third most commonly diagnosed cancer. Patients may receive chemotherapy, targeted therapy, immunotherapy, radiotherapy, and/or surgery. However, not all patients will benefit from each available treatment option. There has been rising interest in personalised medicine, which refers to tailoring treatment plans to the unique characteristics of each patient's cancer. Patient-derived tumour organoids are three-dimensional models of patients' cancer cells which can be tested for sensitivity to various treatment options in the laboratory. This review summarises studies which have explored whether the organoid's sensitivity in the laboratory corresponds to the patient's response in the clinic. Tumour organoids are promising models for personalised medicine in the context of selecting chemotherapy and radiotherapy options. Further advancements in organoid technology are required for testing immunotherapy and certain targeted therapy options. Overall, future clinical trials of organoid testing prior to treatment commencement will support the implementation of organoid-based personalised medicine in the clinic. Colorectal cancer is an important cause of morbidity and mortality worldwide. The current treatment landscape includes chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. A key challenge to improving patient outcomes is the significant inter-patient heterogeneity in treatment response. Tumour organoids derived from the patients' tumours via surgically resected or endoscopically biopsied tissue, have emerged as promising models for personalised medicine. This review synthesises the findings, to date, of studies which have explored the efficacy of ex vivo organoid sensitivity testing for predicting treatment response. Most studies have focused on predicting the response to standard-of-care radiotherapy and chemotherapy options. There is strong evidence to support organoid sensitivity testing of ionising radiation, 5-fluorouracil, and irinotecan, and to a lesser extent, oxaliplatin and TAS-102. Fewer studies have used organoids to identify patients who are likely to benefit from novel treatment options that otherwise remain in clinical trials. This review also summarises recent advancements in organoid culture to include non-epithelial components of the tumour microenvironment, to allow testing of immunotherapy and certain targeted therapy options. Overall, further prospective trials will support the implementation of organoid-based personalised medicine for colorectal cancer patients in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Determining the degree of nodal involvement provides key prognostic information in several malignancies, including colorectal cancer (CRC). Furthermore, predicting long-term outcomes in such cancers often proves challenging to the multidisciplinary team. Therefore, the purpose of this translational research study was to evaluate the role of mi(cro)RNAs as biomarkers used to predict nodal status and recurrence in patients being treated for CRC. This analysis involved the quantification of miRNA targets in 74 patients with CRC using real-time reverse transcriptase polymerase chain reaction. Aberrant expression of miR-21 and miR-135b correlated with increased metastatic disease in local lymph nodes following resection. Interestingly, increased expression of miR-195 displayed strong capabilities of predicting the time to disease recurrence. These results add to the growing evidence illustrating the value of using miRNA expression profiling to inform patient outcomes in cancer. These findings may be further validated in further studies as we attempt to personalise the management paradigm for prospective patients diagnosed with CRC. Background: Approximately one-third of colorectal cancer (CRC) patients will suffer recurrence. MiRNAs are small non-coding RNAs that play important roles in gene expression. We aimed to correlate miRNA expression with aggressive clinicopathological characteristics and survival outcomes in CRC. Methods: Tumour samples were extracted from 74 CRC patients. MiRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Descriptive statistics and Cox regression analyses were performed to correlate miRNA targets with clinicopathological and outcome data. Results: Aberrant miR-21 and miR-135b expression correlate with increased nodal stage (p = 0.039, p = 0.022). Using univariable Cox regression analyses, reduced miR-135b (β-coefficient −1.126, hazard ratio 0.324, standard error (SE) 0.4698, p = 0.017) and increased miR-195 (β-coefficient 1.442, hazard ratio 4.229, SE 0.446, p = 0.001) predicted time to disease recurrence. Survival regression trees analysis illustrated a relative cut-off of ≤0.488 for miR-195 and a relative cut-off of >−0.218 for miR-135b; both were associated with improved disease recurrence (p < 0.001, p = 0.015). Using multivariable analysis with all targets as predictors, miR-195 (β-coefficient 3.187, SE 1.419, p = 0.025) was the sole significant independent predictor of recurrence. Conclusion: MiR-195 has strong value in predicting time to recurrence in CRC patients. Additionally, miR-21 and miR-135b predict the degree nodal burden. Future studies may include these findings to personalize therapeutic and surgical decision making. [ABSTRACT FROM AUTHOR]

Simple Summary: Incisional tissue biopsy is highly invasive, but it remains the current practice for oral cancer diagnosis through histopathological interpretation. To reduce biopsy invasiveness without compromising diagnosis, we pioneered a multigene RT-qPCR method for cancer detection using only a tiny 1 mm3 minimally invasive biopsy. Here we presented international multicohort validation of our second-generation method which involved new genes from matrix/stroma and immune regulations enabling sensitive, quantitative and precise oral cancer detection in otherwise ambiguous oral lesions. Background: Heterogeneity in oral potentially malignant disorder (OPMD) poses a problem for accurate prognosis that impacts on treatment strategy and patient outcome. A holistic assessment based on gene expression signatures from both the tumour cells and their microenvironment is necessary to provide a more precise prognostic assessment than just tumour cell signatures alone. Methods: We reformulated our previously established multigene qPCR test, quantitative Malignancy Index Diagnostic System (qMIDS) with new genes involved in matrix/stroma and immune modulation of the tumour microenvironment. An algorithm calculates and converts a panel of 16 gene mRNA expression levels into a qMIDS index to quantify risk of malignancy for each sample. Results: The new qMIDSV2 assay was validated in a UK oral squamous cell carcinoma (OSCC) cohort (n = 282) of margin and tumour core samples demonstrating significantly better diagnostic performance (AUC = 0.945) compared to previous qMIDSV1 (AUC = 0.759). Performance of qMIDSV2 were independently validated in Chinese (n = 35; AUC = 0.928) and Indian (n = 95; AUC = 0.932) OSCC cohorts. Further, 5-year retrospective analysis on an Indian dysplastic lesion cohort (n = 30) showed that qMIDSV2 was able to significantly differentiate between lesions without transformation and those with malignant transformation. Conclusions: This study validated a novel multi-gene qPCR test on a total of 535 tissue specimens from UK, China and India, demonstrating a rapid minimally invasive method that has a potential application for dysplasia risk stratification. Further study is required to establish if qMIDSV2 could be used to improve OPMD patient management, guide treatment strategy and reduce oral cancer burden. [ABSTRACT FROM AUTHOR]

Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs). [ABSTRACT FROM AUTHOR]

Simple Summary: New therapies for lymphoma continue to be developed at a rapid rate, including for the indolent lymphomas. While traditional cytotoxic chemotherapy remains an effective treatment option, many new treatments target specific aspects of cancer cells such as surface proteins or signaling pathways with the aim of providing a more personalized and tailored approach. By doing so, targeted agents can interrupt cancer cell growth and development, make cancer cells more susceptible to other treatments, or direct the immune system to recognize and destroy cancer cells. This review highlights and discusses the currently available and emerging targeted therapies that apply to follicular lymphoma, lymphoplasmacytic lymphoma/Waldenstrom macroglublinaemia and marginal zone lymphoma. Targeted therapies continue to change the landscape of lymphoma treatment, resulting in improved therapy options and patient outcomes. Numerous agents are now approved for use in the indolent lymphomas and many others under development demonstrate significant promise. In this article, we review the landscape of targeted agents that apply to the indolent lymphomas, predominantly follicular lymphoma, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinaemia and marginal zone lymphoma. The review covers small molecule inhibitors, immunomodulators and targeted immunotherapies, as well as presenting emerging and promising combination therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Mucinous ovarian cancer (MOC) is a rare type of epithelial ovarian cancer, and current treatment regimens for late stage and recurrent disease are inadequate. The 'gold standard' treatments are based on large clinical trials that evaluated potential therapies for all ovarian cancer, but MOC was poorly represented in these studies. As such, what works for most cases may not work for MOC. In this review, we discuss the advances in MOC treatment and explore the concept of theranostics—using therapeutic and diagnostic radionuclides against single cell surface receptors expressed highly in MOC. Additionally, we highlight the previous literature that demonstrates the overexpression of certain targets, exploring their potential to be used as theranostic targets. MOC is a rare histotype of epithelial ovarian cancer, and current management options are inadequate for the treatment of late stage or recurrent disease. A shift towards personalised medicines in ovarian cancer is being observed, with trials targeting specific molecular pathways, however, MOC lags due to its rarity. Theranostics is a rapidly evolving category of personalised medicine, encompassing both a diagnostic and therapeutic approach by recognising targets that are expressed highly in tumour tissue in order to deliver a therapeutic payload. The present review evaluates the protein landscape of MOC in recent immunohistochemical- and proteomic-based research, aiming to identify potential candidates for theranostic application. Fourteen proteins were selected based on cell membrane localisation: HER2, EGFR, FOLR1, RAC1, GPR158, CEACAM6, MUC16, PD-L1, NHE1, CEACAM5, MUC1, ACE2, GP2, and PTPRH. Optimal proteins to target using theranostic agents must exhibit high membrane expression on cancerous tissue with low expression on healthy tissue to afford improved disease outcomes with minimal off-target effects and toxicities. We provide guidelines to consider in the selection of a theranostic target for MOC and suggest future directions in evaluating the results of this review. [ABSTRACT FROM AUTHOR]

Simple Summary: In breast cancer development, the expression of Ki-67 is strongly associated with cancer proliferation and is a known indicator of prognosis and outcome. Ki-67 expression levels are also useful to inform treatment decision making in some cases. As a result, routine measurement of Ki-67 is now widely performed during pathological tumour evaluation. However, the Ki-67 appraisal is not without its limitations and shortcomings—the aim of this study was to provide an overview of Ki-67 use in the clinical setting, the current challenges associated with its measurement, and the novel strategies that will hopefully enhance Ki-67 proliferation indices for prospective breast cancer patients. The advent of molecular medicine has transformed breast cancer management. Breast cancer is now recognised as a heterogenous disease with varied morphology, molecular features, tumour behaviour, and response to therapeutic strategies. These parameters are underpinned by a combination of genomic and immunohistochemical tumour factors, with estrogen receptor (ER) status, progesterone receptor (PgR) status, human epidermal growth factor receptor-2 (HER2) status, Ki-67 proliferation indices, and multigene panels all playing a contributive role in the substratification, prognostication and personalization of treatment modalities for each case. The expression of Ki-67 is strongly linked to tumour cell proliferation and growth and is routinely evaluated as a proliferation marker. This review will discuss the clinical utility, current pitfalls, and promising strategies to augment Ki-67 proliferation indices in future breast oncology. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer remains a significant burden on patients and global health systems. Traditional approaches to therapy have included surgery, and more recently radiation and chemotherapies. Targeted immunotherapies are making significant inroads into improved outcomes, but only for small subsets of patients. Our ability to develop a wider range of targeted therapies rests on our understanding of the molecular pathways involved in carcinogenesis. This review paper summaries our current knowledge of the molecular pathways and druggable targets in head and neck oncology. Head and neck cancers are a heterogeneous group of neoplasms, affecting an ever increasing global population. Despite advances in diagnostic technology and surgical approaches to manage these conditions, survival rates have only marginally improved and this has occurred mainly in developed countries. Some improvements in survival, however, have been a result of new management and treatment approaches made possible because of our ever-increasing understanding of the molecular pathways triggered in head and neck oncogenesis, and the growing understanding of the abundant heterogeneity of this group of cancers. Some important pathways are common to other solid tumours, but their impact on reducing the burden of head and neck disease has been less than impressive. Other less known and little-explored pathways may hold the key to the development of potential druggable targets. The extensive work carried out over the last decade, mostly utilising next generation sequencing has opened up the development of many novel approaches to head and neck cancer treatment. This paper explores our current understanding of the molecular pathways of this group of tumours and outlines associated druggable targets which are deployed as therapeutic approaches in head and neck oncology with the ultimate aim of improving patient outcomes and controlling the personal and economic burden of head and neck cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: B-cell Acute Lymphoblastic Leukaemia is one of the most common cancers in childhood, with 20% of patients eventually relapsing. Flow cytometry is routinely used for diagnosis and follow-up, but it currently does not provide prognostic value at diagnosis. The volume and the high-dimensional character of this data makes it ideal for its exploitation by means of Artificial Intelligence methods. We collected flow cytometry data from 56 patients from two hospitals. We analysed differences in intensity of marker expression in order to predict relapse at the moment of diagnosis. We finally correlated this data with biomolecular information, constructing a classifier based on CD38 expression. Artificial intelligence methods may help in unveiling information that is hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data, but they have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell Acute Lymphoblastic Leukaemia. In this paper, we analysed flow cytometry data that were obtained at diagnosis from 56 paediatric B-cell Acute Lymphoblastic Leukaemia patients from two local institutions. Our aim was to assess the prognostic potential of immunophenotypical marker expression intensity. We constructed classifiers that are based on the Fisher's Ratio to quantify differences between patients with relapsing and non-relapsing disease. We also correlated this with genetic information. The main result that arises from the data was the association between subexpression of marker CD38 and the probability of relapse. [ABSTRACT FROM AUTHOR]

Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone within these cancers. The application of molecular profiling techniques, together with animal model systems and engineered cell-lines has enabled the identification of a series of potential bone-metastasis biomarker molecules predictive of bone metastasis risk. Some of these biomarker candidates have been validated within patient-derived samples providing a step towards clinical utility. Recent developments in multiplex biomarker quantification now enable the simultaneous measurement of up to 96 micro-RNA/protein molecules in a spatially defined manner with single-cell resolution, thus enabling the characterisation of the key molecules active at the sites of pre-metastatic niche formation as well as tumour-stroma signalling. These technologies have considerable potential to inform biomarker discovery. Additionally, a potential future extension of these discoveries could also be the identification of novel drug targets within cancer spread to bone. This chapter summarises recent findings in biomarker discovery within the key bone metastatic cancers (breast, prostate, lung and renal cell carcinoma). Tissue-based and circulating blood-based biomarkers are discussed from the fields of genomics, epigenetic regulation (micro-RNAs) and protein/cell-signalling together with a discussion of the potential future development of these markers towards clinical development. [ABSTRACT FROM AUTHOR]

Artificial intelligence methods may help in unveiling information that is hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data, but they have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell Acute Lymphoblastic Leukaemia. In this paper, we analysed flow cytometry data that were obtained at diagnosis from 56 paediatric B-cell Acute Lymphoblastic Leukaemia patients from two local institutions. Our aim was to assess the prognostic potential of immunophenotypical marker expression intensity. We constructed classifiers that are based on the Fisher's Ratio to quantify differences between patients with relapsing and non-relapsing disease. We also correlated this with genetic information. The main result that arises from the data was the association between subexpression of marker CD38 and the probability of relapse.