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  1. Article ; Online: KRASG12C mutant lung adenocarcinoma: unique biology, novel therapies and new challenges.

    Moldvay, Judit / Tímár, József

    Pathology oncology research : POR

    2024  Volume 29, Page(s) 1611580

    Abstract: KRAS mutant lung cancer is the most prevalent molecular subclass of adenocarcinoma (LUAD), which is a heterogenous group depending on the mutation-type which affects not only the function of the oncogene but affects the biological behavior of the cancer ... ...

    Abstract KRAS mutant lung cancer is the most prevalent molecular subclass of adenocarcinoma (LUAD), which is a heterogenous group depending on the mutation-type which affects not only the function of the oncogene but affects the biological behavior of the cancer as well. Furthermore, KRAS mutation affects radiation sensitivity but leads also to bevacizumab and bisphosphonate resistance as well. It was highly significant that allele specific irreversible inhibitors have been developed for the smoking associated G12C mutant KRAS (sotorasib and adagrasib). Based on trial data both sotorasib and adagrasib obtained conditional approval by FDA for the treatment of previously treated advanced LUAD. Similar to other target therapies, clinical administration of KRASG12C inhibitors (sotorasib and adagrasib) resulted in acquired resistance due to various genetic changes not only in KRAS but in other oncogenes as well. Recent clinical studies are aiming to increase the efficacy of G12C inhibitors by novel combination strategies.
    MeSH term(s) Humans ; Proto-Oncogene Proteins p21(ras)/genetics ; Adenocarcinoma of Lung/drug therapy ; Adenocarcinoma of Lung/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mutation ; Biology ; Acetonitriles ; Piperazines ; Pyrimidines
    Chemical Substances adagrasib (8EOO6HQF8Y) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Acetonitriles ; Piperazines ; Pyrimidines
    Language English
    Publishing date 2024-01-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1375979-6
    ISSN 1532-2807 ; 1219-4956
    ISSN (online) 1532-2807
    ISSN 1219-4956
    DOI 10.3389/pore.2023.1611580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A hasnyálmirigyrák molekuláris klasszifikációja.

    Tímár, József

    Magyar onkologia

    2021  Volume 65, Issue 3, Page(s) 201–205

    Abstract: Pancreatic cancer is a malignancy with outstandingly poor prognosis caused by several factors among which one is that it is predominated by mutant KRAS oncogene. Genomic studies revealed that clinically useful therapy targets are present only in the DNA ... ...

    Title translation Molecular classification of pancreatic cancer.
    Abstract Pancreatic cancer is a malignancy with outstandingly poor prognosis caused by several factors among which one is that it is predominated by mutant KRAS oncogene. Genomic studies revealed that clinically useful therapy targets are present only in the DNA repair deficient subgroup and in the minor wild type KRAS-carrying group. However, phylogenetic studies defined four molecular subgroups of pancreatic cancer among which the immunogenic progenitor form could well be the target of immunotherapies. Furthermore, this group may well be the one characterized by DNA repair deficiency and high tumor mutational burden. Furthermore, the majority of familiar pancreatic cancers could also be found in this latter subgroup. Unfortunately, the G12C mutation of KRAS in pancreatic cancer is rare, therefore pancreatic cancer patients could not benefit from the recent revolution of KRAS target therapies.
    MeSH term(s) Genomics ; Humans ; Pancreatic Neoplasms/genetics ; Phylogeny
    Language Hungarian
    Publishing date 2021-08-10
    Publishing country Hungary
    Document type Journal Article
    ZDB-ID 414033-3
    ISSN 2060-0399 ; 0025-0244
    ISSN (online) 2060-0399
    ISSN 0025-0244
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  3. Article ; Online: Guest editorial/preface.

    Tímár, József

    Cancer metastasis reviews

    2020  Volume 39, Issue 4, Page(s) 1017

    MeSH term(s) Humans ; Mutation ; Neoplasms/enzymology ; Neoplasms/genetics ; Proto-Oncogene Proteins p21(ras)/genetics
    Chemical Substances KRAS protein, human ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2020-09-16
    Publishing country Netherlands
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 604857-2
    ISSN 1573-7233 ; 0167-7659
    ISSN (online) 1573-7233
    ISSN 0167-7659
    DOI 10.1007/s10555-020-09933-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A daganatok öröklődésének molekuláris alapjai.

    Tímár, József

    Magyar onkologia

    2020  Volume 64, Issue 1, Page(s) 7–11

    Abstract: Cancer susceptibility but not specific cancer types can be inherited. This susceptibility(ies) is due to inherited germline mutations of key genes of the controllers of genome integrity, translational control, the cell cycle regulation or even the tumor ... ...

    Title translation Molecular basis of hereditary cancers.
    Abstract Cancer susceptibility but not specific cancer types can be inherited. This susceptibility(ies) is due to inherited germline mutations of key genes of the controllers of genome integrity, translational control, the cell cycle regulation or even the tumor vascularization. Cancer susceptibility can be manifested in various forms of specific syndromes, each associated with different alterations of genes. Most of these genes are tumor suppressors, and the mutations affect one or both alleles. Interestingly, inherited mutations of oncogenes resulting in cancer susceptibility are much rarer, typically affect only one allele, and the inheritance is dominant. However, cancer susceptibility is influenced not only by high penetrance gene defects but also by inherited low penetrance gene mutations, complicating the effective identification of affected individuals and their families.
    MeSH term(s) Genetic Predisposition to Disease ; Germ-Line Mutation/genetics ; Humans ; Neoplasms/genetics ; Oncogenes/genetics
    Language Hungarian
    Publishing date 2020-01-13
    Publishing country Hungary
    Document type Journal Article ; Review
    ZDB-ID 414033-3
    ISSN 2060-0399 ; 0025-0244
    ISSN (online) 2060-0399
    ISSN 0025-0244
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  5. Article: Metastatic Progression of Human Melanoma.

    Tímár, József / Ladányi, Andrea

    Cancers

    2023  Volume 15, Issue 4

    Abstract: This Topical Collection, comprising 13 papers (10 original articles and 3 reviews), addresses various aspects of the field of melanoma progression: genomic and proteomic approaches, experimental studies, the questions of sentinel lymph node dissection, ... ...

    Abstract This Topical Collection, comprising 13 papers (10 original articles and 3 reviews), addresses various aspects of the field of melanoma progression: genomic and proteomic approaches, experimental studies, the questions of sentinel lymph node dissection, and metastasis formation of uveal and conjunctival melanomas is also discussed [...].
    Language English
    Publishing date 2023-02-15
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15041225
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  6. Article ; Online: Editorial: Pathology and Oncology Research: addressing publication ethics issues.

    Tímár, József / Ladányi, Andrea / Sebestyén, Anna / Kopper, László

    Pathology oncology research : POR

    2024  Volume 30, Page(s) 1611691

    MeSH term(s) Humans ; Medical Oncology ; Biomedical Research
    Language English
    Publishing date 2024-02-14
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 1375979-6
    ISSN 1532-2807 ; 1219-4956
    ISSN (online) 1532-2807
    ISSN 1219-4956
    DOI 10.3389/pore.2024.1611691
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  7. Article ; Online: A CUP (Cancer of Unknown Primary) daganatok patológiai diagnosztikája.

    Tímár, József

    Magyar onkologia

    2019  Volume 63, Issue 2, Page(s) 67–74

    Abstract: CUP (Cancer of Unknown Primary) is a relatively frequent cancer type causing incomparable difficulties in pathological diagnosis as compared to other tumor types. The primary may even remain unknown at authopsy due to microscopic size or previous ... ...

    Title translation Pathological diagnostics of CUP (Cancer of Unknown Primary).
    Abstract CUP (Cancer of Unknown Primary) is a relatively frequent cancer type causing incomparable difficulties in pathological diagnosis as compared to other tumor types. The primary may even remain unknown at authopsy due to microscopic size or previous regression. By applying the biological, epidemiological cancer information it is possible to compose rational pathological differential diagnostic algorithms to define with high probability the primary site of the cancer. The new molecular tests developed for CUP are very helpful especially if they are used in combination with pathological data.
    MeSH term(s) Algorithms ; Diagnosis, Differential ; Humans ; Neoplasms, Unknown Primary/diagnosis ; Neoplasms, Unknown Primary/pathology
    Language Hungarian
    Publishing date 2019-03-30
    Publishing country Hungary
    Document type Journal Article ; Review
    ZDB-ID 414033-3
    ISSN 2060-0399 ; 0025-0244
    ISSN (online) 2060-0399
    ISSN 0025-0244
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  8. Article ; Online: A prosztatarák molekuláris patológiája.

    Tímár, József

    Magyar onkologia

    2019  Volume 63, Issue 1, Page(s) 5–9

    Abstract: Prostate cancer seems to be two diseases: a localized early cancer and a castration-resistant metastatic cancer. While in the localized form the most prevalent genetic alterations are the translocations of the ETS genes, in the castration-resistant form ... ...

    Title translation Molecular pathology of prostate cancer.
    Abstract Prostate cancer seems to be two diseases: a localized early cancer and a castration-resistant metastatic cancer. While in the localized form the most prevalent genetic alterations are the translocations of the ETS genes, in the castration-resistant form the most prevalent genetic alteration affects androgen receptor and oncosuppressors TP53 and PTEN. The main drivers of the genetic progression of prostate cancer are defects of the DNA-repair systems which are also responsible for the familiar disease. Several prognostic genomic classifiers have been developed and validated clinically which are able to guide management of the early diseases. Today the most useful predictive genetic testing is that of the androgen receptor but others are becoming equally important which can predict taxane resistance.
    MeSH term(s) Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Genetic Testing ; Humans ; Male ; PTEN Phosphohydrolase/genetics ; Pathology, Molecular ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics ; Prostatic Neoplasms, Castration-Resistant/pathology ; Receptors, Androgen/genetics ; Tumor Suppressor Protein p53/genetics
    Chemical Substances Receptors, Androgen ; TP53 protein, human ; Tumor Suppressor Protein p53 ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
    Language Hungarian
    Publishing date 2019-01-02
    Publishing country Hungary
    Document type Journal Article ; Review
    ZDB-ID 414033-3
    ISSN 2060-0399 ; 0025-0244
    ISSN (online) 2060-0399
    ISSN 0025-0244
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  9. Article ; Online: On-Target Side Effects of Targeted Therapeutics of Cancer.

    Tímár, József / Uhlyarik, Andrea

    Pathology oncology research : POR

    2022  Volume 28, Page(s) 1610694

    Abstract: The concept of precision medicine is based on the identification of hallmarks of cancer to exploit them as drug targets. The basic idea was that in this way the therapeutic modalities will be more effective and the side effects will be less. Since the ... ...

    Abstract The concept of precision medicine is based on the identification of hallmarks of cancer to exploit them as drug targets. The basic idea was that in this way the therapeutic modalities will be more effective and the side effects will be less. Since the majority of these novel modalities are not specific for a cancer-related biological process or a cancer-specific (mutant) target protein, it is not a surprise that we had to learn new type of side effects, because these therapeutics also affect physiological or pathological processes. Even more, in cases of some of these novel therapies we were able to discover new molecular mechanisms of physiological and pathological processes. Identification of the on-target side effects of targeted drugs can help to prevent the development of them or better manage the patients when emerge during cancer therapy.
    MeSH term(s) Drug-Related Side Effects and Adverse Reactions ; Humans ; Molecular Targeted Therapy/adverse effects ; Neoplasms/drug therapy
    Language English
    Publishing date 2022-09-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1375979-6
    ISSN 1532-2807 ; 1219-4956
    ISSN (online) 1532-2807
    ISSN 1219-4956
    DOI 10.3389/pore.2022.1610694
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  10. Article ; Online: A bőr melanómájának molekuláris patológiája: diagnosztikus, prognosztikus és prediktív markerek.

    Tímár, József / Ladányi, Andrea

    Magyar onkologia

    2022  Volume 66, Issue 2, Page(s) 101–108

    Abstract: Skin melanoma became one of the most frequent malignancies of the skin mainly due to the increased exposure to environmental UV irradiation. However, this did not lead to the increase of mortality, mainly due to the efficient early diagnostics as well as ...

    Title translation Molecular pathology of skin melanoma.
    Abstract Skin melanoma became one of the most frequent malignancies of the skin mainly due to the increased exposure to environmental UV irradiation. However, this did not lead to the increase of mortality, mainly due to the efficient early diagnostics as well as to the development of new therapies which were based on the identification of the mutation patterns and understanding of the immunobiology. Molecular markers are important to differentiate malignant tumors from precancerous ones but also routinely available to define prognosis. Immunotherapy can be used in any molecular class of melanoma, while target therapy is only available in case of BRAF mutant form. Meanwhile these novel therapies induce new resistance mechanisms based on the development of acquired genetic alterations. Due to these facts the initial molecular profiling of the resected primary tumors must gradually be replaced by continuous monitoring.
    MeSH term(s) Humans ; Melanoma/genetics ; Melanoma/pathology ; Melanoma/therapy ; Pathology, Molecular ; Proto-Oncogene Proteins B-raf/genetics ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Skin Neoplasms/therapy ; Melanoma, Cutaneous Malignant
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
    Language Hungarian
    Publishing date 2022-05-03
    Publishing country Hungary
    Document type Journal Article
    ZDB-ID 414033-3
    ISSN 2060-0399 ; 0025-0244
    ISSN (online) 2060-0399
    ISSN 0025-0244
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