Dataset Information

Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics.

ABSTRACT: Cancer is a group of diseases causing abnormal cell growth, altering the genome, and invading or spreading to other parts of the body. Among therapeutic peptide drugs, anticancer peptides (ACPs) have been considered to target and kill cancer cells because cancer cells have unique characteristics such as a high negative charge and abundance of microvilli in the cell membrane when compared to a normal cell. ACPs have several advantages, such as high specificity, cost-effectiveness, low immunogenicity, minimal toxicity, and high tolerance under normal physiological conditions. However, the development and identification of ACPs are time-consuming and expensive in traditional wet-lab-based approaches. Thus, the application of artificial intelligence on the approaches can save time and reduce the cost to identify candidate ACPs. Recently, machine learning (ML), deep learning (DL), and hybrid learning (ML combined DL) have emerged into the development of ACPs without experimental analysis, owing to advances in computer power and big data from the power system. Additionally, we suggest that combination therapy with classical approaches and ACPs might be one of the impactful approaches to increase the efficiency of cancer therapy.

SUBMITTER: Hwang JS

PROVIDER: S-EPMC9147327 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics.

Hwang Ji Su JS Kim Seok Gi SG Shin Tae Hwan TH Jang Yong Eun YE Kwon Do Hyeon DH Lee Gwang G

Pharmaceutics 20220506 5

Cancer is a group of diseases causing abnormal cell growth, altering the genome, and invading or spreading to other parts of the body. Among therapeutic peptide drugs, anticancer peptides (ACPs) have been considered to target and kill cancer cells because cancer cells have unique characteristics such as a high negative charge and abundance of microvilli in the cell membrane when compared to a normal cell. ACPs have several advantages, such as high specificity, cost-effectiveness, low immunogenic ...[more]

PMID: 35631583

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Project description:BackgroundRisk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability. We aimed to examine an application of artificial intelligence (AI) to ECG images as a surrogate for imaging risk biomarkers and its association with early CTRCD.MethodsAcross a US-based health system (2013-2023), we identified 1550 patients (aged, 60 [interquartile range, 51-69] years, 1223 [78.9%] women) without cardiomyopathy who received anthracyclines or trastuzumab for breast cancer or non-Hodgkin lymphoma and had ECG performed ≤12 months before treatment. We deployed a validated AI model of left ventricular systolic dysfunction to baseline ECG images and defined low-, intermediate-, and high-risk groups based on AI-ECG left ventricular systolic dysfunction probabilities of <0.01, 0.01 to 0.1, and ≥0.1 (positive screen), respectively. We explored the association with early CTRCD (new cardiomyopathy, heart failure, or left ventricular ejection fraction <50%), or left ventricular ejection fraction <40%, up to 12 months after treatment. In a mechanistic analysis, we assessed the association between global longitudinal strain and AI-ECG left ventricular systolic dysfunction probabilities in studies performed within 15 days of each other.ResultsAmong 1550 patients without known cardiomyopathy (median follow-up, 14.1 [interquartile range, 13.4-17.1] months), 83 (5.4%), 562 (36.3%), and 905 (58.4%) were classified as high, intermediate, and low risk, respectively, by baseline AI-ECG. A high-risk versus low-risk AI-ECG screen (≥0.1 versus <0.01) was associated with a 3.4-fold and 13.5-fold higher incidence of CTRCD (adjusted hazard ratio, 3.35 [95% CI, 2.25-4.99]) and left ventricular ejection fraction <40% (adjusted hazard ratio, 13.52 [95% CI, 5.06-36.10]), respectively. Post hoc analyses supported longitudinal increases in AI-ECG probabilities within 6 to 12 months of a CTRCD event. Among 1428 temporally linked echocardiograms and ECGs, AI-ECG left ventricular systolic dysfunction probabilities were associated with worse global longitudinal strain (global longitudinal strain, -19% [interquartile range, -21% to -17%] for probabilities <0.1, to -15% [interquartile range, -15% to -9%] for ≥0.5 [P<0.001]).ConclusionsAI applied to baseline ECG images can stratify the risk of early CTRCD associated with anthracycline or trastuzumab exposure in the setting of breast cancer and non-Hodgkin lymphoma therapy.

Project description:BACKGROUND: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life, and there remain no validated predictive models to guide its use. METHODS: We used digital pathology images from pretreatment prostate tissue and clinical data from 5727 patients enrolled in five phase 3 randomized trials, in which treatment was radiotherapy with or without ADT, as our data source to develop and validate an artificial intelligence (AI)–derived predictive patient-specific model that would determine which patients would develop the primary end point of distant metastasis. The model used baseline data to provide a binary output that a given patient will likely benefit from ADT or not. After the model was locked, validation was performed using data from NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 (n=1594), a trial that randomly assigned men to radiotherapy plus or minus 4 months of ADT. Fine–Gray regression and restricted mean survival times were used to assess the interaction between treatment and the predictive model and within predictive model–positive, i.e., benefited from ADT, and –negative subgroup treatment effects. RESULTS: Overall, in the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis. Of these enrolled patients, 543 (34%) were model positive, and ADT significantly reduced the risk of distant metastasis compared with radiotherapy alone. Of 1051 patients who were model negative, ADT did not provide benefit. CONCLUSIONS: Our AI-based predictive model was able to identify patients with a predominantly intermediate risk for prostate cancer likely to benefit from short-term ADT. (Supported by a grant [U10CA180822] from NRG Oncology Statistical and Data Management Center, a grant [UG1CA189867] from NCI Community Oncology Research Program, a grant [U10CA180868] from NRG Oncology Operations, and a grant [U24CA196067] from NRG Specimen Bank from the National Cancer Institute and by Artera, Inc. ClinicalTrials.gov numbers NCT00767286, NCT00002597, NCT00769548, NCT00005044, and NCT00033631.)

Dataset Information

Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics.

Publications

Development of Anticancer Peptides Using Artificial Intelligence and Combinational Therapy for Cancer Therapeutics.

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