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  1. Article: Cytotoxic and targeted therapy for BRCA1/2-driven cancers.

    Imyanitov, Evgeny N

    Hereditary cancer in clinical practice

    2021  Volume 19, Issue 1, Page(s) 36

    Abstract: Tumors arising in BRCA1/2 germline mutation carriers usually demonstrate somatic loss of the remaining BRCA1/2 allele and increased sensitivity to platinum compounds, anthracyclines, mitomycin C and poly (ADP-ribose) polymerase inhibitors (PARPi). ... ...

    Abstract Tumors arising in BRCA1/2 germline mutation carriers usually demonstrate somatic loss of the remaining BRCA1/2 allele and increased sensitivity to platinum compounds, anthracyclines, mitomycin C and poly (ADP-ribose) polymerase inhibitors (PARPi). Exposure to conventional platinum-based therapy or PARPi results in the restoration of BRCA1/2 function and development of resistance to systemic therapy, therefore, there is a need for other treatment options. Some studies suggested that the use of specific drug combinations or administration of high-dose chemotherapy may result in pronounced tumor responses. BRCA1/2-driven tumors are characterized by increased immunogenicity; promising efficacy of immune therapy has been demonstrated in a number of preclinical and clinical investigations. There are outstanding issues, which require further consideration. Platinum compounds and PARPi have very similar mode of antitumor action and are likely to render cross-resistance to each other, so their optimal position in cancer treatment schemes may be a subject of additional studies. Sporadic tumors with somatically acquired inactivation of BRCA1/2 or related genes resemble hereditary neoplasms with regard to the spectrum of drug sensitivity; the development of user-friendly BRCAness tests presents a challenge. Many therapeutic decisions are now based on the BRCA1/2 status, so the significant reduction of the turn-around time for predictive laboratory assays is of particular importance.
    Language English
    Publishing date 2021-08-28
    Publishing country Poland
    Document type Journal Article ; Review
    ZDB-ID 2252512-9
    ISSN 1897-4287 ; 1731-2302
    ISSN (online) 1897-4287
    ISSN 1731-2302
    DOI 10.1186/s13053-021-00193-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hereditary Conditions Associated with Elevated Cancer Risk in Childhood.

    Suspitsin, Evgeny N / Imyanitov, Evgeny N

    Biochemistry. Biokhimiia

    2023  Volume 88, Issue 7, Page(s) 880–891

    Abstract: Received January, 31, 2023 Revised March, 16, 2023 Accepted March, 18, 2023 Widespread use of the next-generation sequencing (NGS) technologies revealed that a significant percentage of tumors in children develop as a part of monogenic hereditary ... ...

    Abstract Received January, 31, 2023 Revised March, 16, 2023 Accepted March, 18, 2023 Widespread use of the next-generation sequencing (NGS) technologies revealed that a significant percentage of tumors in children develop as a part of monogenic hereditary diseases. Predisposition to the development of pediatric neoplasms is characteristic of a wide range of conditions including hereditary tumor syndromes, primary immunodeficiencies, RASopathies, and phakomatoses. The mechanisms of tumor molecular pathogenesis are diverse and include disturbances in signaling cascades, defects in DNA repair, chromatin remodeling, and microRNA processing. Timely diagnosis of tumor-associated syndromes is important for the proper choice of cancer treatment, genetic counseling of families, and development of the surveillance programs. The review describes the spectrum of neoplasms characteristic of the most common syndromes and molecular pathogenesis of these diseases.
    Language English
    Publishing date 2023-09-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297923070039
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Hereditary Renal Cancer Syndromes.

    Yanus, Grigory A / Kuligina, Ekaterina Sh / Imyanitov, Evgeny N

    Medical sciences (Basel, Switzerland)

    2024  Volume 12, Issue 1

    Abstract: Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances ...

    Abstract Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances of RCC predisposition are attributed to the loss-of-function mutations in tumor suppressor genes, which drive the malignant progression via somatic inactivation of the remaining allele. These syndromes almost always have extrarenal manifestations, for example, von Hippel-Lindau (VHL) disease, fumarate hydratase tumor predisposition syndrome (FHTPS), Birt-Hogg-Dubé (BHD) syndrome, tuberous sclerosis (TS), etc. In contrast to the above conditions, hereditary papillary renal cell carcinoma syndrome (HPRCC) is caused by activating mutations in the
    MeSH term(s) Humans ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; Carcinoma, Renal Cell/therapy ; Tuberous Sclerosis/genetics ; Neoplastic Syndromes, Hereditary/genetics ; Neoplastic Syndromes, Hereditary/therapy ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Kidney Neoplasms/therapy ; Kidney/pathology ; Birt-Hogg-Dube Syndrome/genetics ; von Hippel-Lindau Disease/genetics ; von Hippel-Lindau Disease/therapy
    Language English
    Publishing date 2024-02-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2754473-4
    ISSN 2076-3271 ; 2076-3271
    ISSN (online) 2076-3271
    ISSN 2076-3271
    DOI 10.3390/medsci12010012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution.

    Aleksakhina, Svetlana N / Ivantsov, Alexander O / Imyanitov, Evgeny N

    International journal of molecular sciences

    2024  Volume 25, Issue 7

    Abstract: Many tumors have well-defined vulnerabilities, thus potentially allowing highly specific and effective treatment. There is a spectrum of actionable genetic alterations which are shared across various tumor types and, therefore, can be targeted by a given ...

    Abstract Many tumors have well-defined vulnerabilities, thus potentially allowing highly specific and effective treatment. There is a spectrum of actionable genetic alterations which are shared across various tumor types and, therefore, can be targeted by a given drug irrespective of tumor histology. Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for
    MeSH term(s) Humans ; B7-H1 Antigen ; BRCA1 Protein ; Protein-Tyrosine Kinases ; BRCA2 Protein ; Proto-Oncogene Proteins ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Neoplasms/drug therapy ; Neoplasms/genetics
    Chemical Substances BRCA1 protein, human ; B7-H1 Antigen ; BRCA1 Protein ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; BRCA2 protein, human ; BRCA2 Protein ; Proto-Oncogene Proteins ; Antineoplastic Agents
    Language English
    Publishing date 2024-04-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25074094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Northern origin of the BRCA2 c.5286 T > G founder allele.

    Yanus, Grigory A / Sokolenko, Anna P / Imyanitov, Evgeny N

    Breast cancer research and treatment

    2023  Volume 204, Issue 1, Page(s) 191

    MeSH term(s) Humans ; Female ; Alleles ; Breast Neoplasms/genetics ; BRCA2 Protein/genetics ; Genes, BRCA2 ; Founder Effect ; Mutation ; Ovarian Neoplasms/genetics ; Genetic Predisposition to Disease ; BRCA1 Protein/genetics
    Chemical Substances BRCA2 Protein ; BRCA1 Protein ; BRCA2 protein, human
    Language English
    Publishing date 2023-12-07
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 604563-7
    ISSN 1573-7217 ; 0167-6806
    ISSN (online) 1573-7217
    ISSN 0167-6806
    DOI 10.1007/s10549-023-07202-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Neoadjuvant therapy for ovarian cancer.

    Imyanitov, Evgeny N

    Chinese clinical oncology

    2018  Volume 7, Issue 6, Page(s) 54

    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemotherapy, Adjuvant ; Female ; Humans ; Neoadjuvant Therapy ; Ovarian Neoplasms/drug therapy ; Prognosis
    Language English
    Publishing date 2018-10-23
    Publishing country China
    Document type Journal Article
    ZDB-ID 2828547-5
    ISSN 2304-3873 ; 2304-3865
    ISSN (online) 2304-3873
    ISSN 2304-3865
    DOI 10.21037/cco.2018.10.07
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives.

    Aleksakhina, Svetlana N / Imyanitov, Evgeny N

    International journal of molecular sciences

    2021  Volume 22, Issue 20

    Abstract: The administration of many cancer drugs is tailored to genetic tests. Some genomic events, e.g., alterations of EGFR or BRAF oncogenes, result in the conformational change of the corresponding proteins and call for the use of mutation-specific compounds. ...

    Abstract The administration of many cancer drugs is tailored to genetic tests. Some genomic events, e.g., alterations of EGFR or BRAF oncogenes, result in the conformational change of the corresponding proteins and call for the use of mutation-specific compounds. Other genetic perturbations, e.g., HER2 amplifications, ALK translocations or MET exon 14 skipping mutations, cause overproduction of the entire protein or its kinase domain. There are multilocus assays that provide integrative characteristics of the tumor genome, such as the analysis of tumor mutation burden or deficiency of DNA repair. Treatment planning for non-small cell lung cancer requires testing for EGFR, ALK, ROS1, BRAF, MET, RET and KRAS gene alterations. Colorectal cancer patients need to undergo KRAS, NRAS, BRAF, HER2 and microsatellite instability analysis. The genomic examination of breast cancer includes testing for HER2 amplification and PIK3CA activation. Melanomas are currently subjected to BRAF and, in some instances, KIT genetic analysis. Predictive DNA assays have also been developed for thyroid cancers, cholangiocarcinomas and urinary bladder tumors. There is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor types. The invention of genomically tailored treatment has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; DNA Repair/genetics ; ErbB Receptors/genetics ; Genetic Testing/methods ; Humans ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics
    Chemical Substances Antineoplastic Agents ; KRAS protein, human ; ErbB Receptors (EC 2.7.10.1) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2021-10-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms222010931
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Molecular tests for prediction of tumor sensitivity to cytotoxic drugs.

    Imyanitov, Evgeny N / Iyevleva, Aglaya G

    Cancer letters

    2021  Volume 526, Page(s) 41–52

    Abstract: Chemotherapy constitutes the backbone of cancer treatment. Several predictive assays assist personalized administration of cytotoxic drugs and are recommended for use in a clinical setting. The deficiency of DNA repair by homologous recombination (HRD), ... ...

    Abstract Chemotherapy constitutes the backbone of cancer treatment. Several predictive assays assist personalized administration of cytotoxic drugs and are recommended for use in a clinical setting. The deficiency of DNA repair by homologous recombination (HRD), which is caused by inactivation of BRCA1/2 genes or other genetic events, is associated with high tumor responsiveness to platinum compounds, bifunctional alkylating agents and topoisomerase II poisons. Low activity of MGMT predicts the efficacy of nitrosoureas and tetrazines. Some clinically established pharmacogenetic tests allow for the adjustment of drug dosage, for example, the analysis of DPYD allelic variants for administration of fluoropyrimidines and UGT1A1 genotyping for the use of irinotecan. While there are promising molecular predictors of tumor sensitivity to pemetrexed, gemcitabine and taxanes, they remain in the investigational stage and require additional validation. Comprehensive molecular analysis of tumors obtained from drug responders and non-responders is likely to reveal new clinically useful predictive markers for cytotoxic therapy.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Humans ; Neoplasms/drug therapy
    Chemical Substances Antineoplastic Agents
    Language English
    Publishing date 2021-11-20
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2021.11.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Unexpected "Lazarus response" to single-agent bevacizumab in heavily pretreated patients with HER2-positive breast cancer.

    Emshanov, Alexey V / Nesterov, Denis V / Sokolova, Tatyana N / Amankwah, Priscilla S / Imyanitov, Evgeny N

    Exploration of targeted anti-tumor therapy

    2023  Volume 4, Issue 6, Page(s) 1157–1164

    Abstract: Early clinical trials aimed to halt cancer progression by inhibiting the growth of new blood vessels in tumors through single-agent targeted therapy with bevacizumab. These trials largely proved unsuccessful. However, bevacizumab turned out to be ... ...

    Abstract Early clinical trials aimed to halt cancer progression by inhibiting the growth of new blood vessels in tumors through single-agent targeted therapy with bevacizumab. These trials largely proved unsuccessful. However, bevacizumab turned out to be efficient when administered in combination with other anticancer drugs. The efficacy of this approach is explained by the ability of bevacizumab to eliminate immature blood vessels thus normalizing intratumoral blood flow and improving the delivery of cytotoxic or targeted agents. This report describes four cases of heavily pretreated patients with metastatic HER2-positive breast cancer, who had no meaningful treatment options left, and who received single-agent bevacizumab as an empirical last-resort therapy. Three of these patients had severe complaints, and they demonstrated striking symptomatic relief within the first day of this treatment. In addition to the observed "Lazarus response", which was likely attributed to the bevacizumab-driven resolution of edema, some evidence of a direct antitumor effect was observed. These data may call for the reconsideration of bevacizumab monotherapy in patients with HER2-associated breast cancer, and perhaps in some other categories of cancer patients.
    Language English
    Publishing date 2023-12-06
    Publishing country United States
    Document type Case Reports
    ISSN 2692-3114
    ISSN (online) 2692-3114
    DOI 10.37349/etat.2023.00189
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Integration of the blood test into the low-dose computed tomography lung cancer screening: reliable discrimination between malignant and non-malignant radiographic findings.

    Kuligina, Ekaterina S / Iyevleva, Aglaya G / Imyanitov, Evgeny N

    Translational lung cancer research

    2021  Volume 10, Issue 10, Page(s) 4035–4038

    Language English
    Publishing date 2021-11-23
    Publishing country China
    Document type Editorial ; Comment
    ZDB-ID 2754335-3
    ISSN 2226-4477 ; 2218-6751
    ISSN (online) 2226-4477
    ISSN 2218-6751
    DOI 10.21037/tlcr-21-680
    Database MEDical Literature Analysis and Retrieval System OnLINE

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