New horizons from novel therapies in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment

Blastic Plasmacytoid Dendritic Cell Neoplasm without Cutaneous Manifestation: A Case Report.

BACKGROUND As an uncommon malignancy with the highest prevalence in the elderly population, blastic plasmacytoid dendritic cell neoplasm or BPDCN is a hematologic disorder with unknown pathogenesis and devastating outcomes. This neoplasm usually manifests in the skin but can also involve the bone marrow, and less frequently the central nervous system (CNS). However, it does not exclude other organs and can even be associated with other malignancies. CASE REPORT Here, we discuss an interesting case of BPDCN in an 85-year-old man who mainly presented with dizziness and weakness. Physical examination revealed splenomegaly, laboratory tests showed pancytopenia, and peripheral blood smear depicted metamyelocytes. Further workup including bone marrow biopsy revealed atypical cells and flow cytometry disclosed 84% blasts positive for cluster of differentiation (CD) 4, CD53, and CD156 suggestive of BPDCN. Moreover, cerebrospinal fluid (CSF) studies came back positive for tumor plasmacytoid dendritic cells. The patient underwent chemotherapy with CHOP, mini-CHOP regimens, and venetoclax, as well as treatment for CNS involvement. He achieved remission, but unfortunately had a recurrence of the disease. Later he was admitted due to pneumonia with concomitant recurrent pulmonary effusions complicated by multiorgan dysfunction and subsequently died. CONCLUSIONS The diagnosis of BPDCN can be very challenging, and high clinical suspicion and intuition are required to reach the diagnosis, especially when patients do not present with cutaneous involvement. Concerning treatment options, novel therapies such as tagraxofusp, a CD123-directed cytotoxin, are emerging in the hope of decreasing the rate of mortality for this aggressive malignancy

New Horizons from Novel Therapies in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment

Nowe perspektywy leczenia złośliwego międzybłoniaka opłucnej

Złośliwy międzybłoniak opłucnej to stosunkowo rzadko występująca choroba rozrostowa komórek mezotelialnych opłucnej, cechująca się dużą śmiertelnością. Jej patogeneza nieodłącznie wiąże się z ekspozycją na działanie azbestu. I chociaż coraz więcej wiadomo na ten temat, nadal wiele zagadnień dotyczących mechanizmu powstawania i rozwoju złośliwego międzybłoniaka opłucnej pozostaje niejasnych. Terapia trójmodalna, składająca się z leczenia chirurgicznego skojarzonego z chemioterapią i/lub radioterapią, nadal pozostaje terapią standardową. Rozwój oporności komórek guza na radioterapię oraz niektóre środki chemioterapeutyczne bardzo utrudniają leczenie tego nowotworu. Promieniowanie jonizujące uszkadza DNA komórek nowotworowych i zwiększa odpowiedź na leczenie, lecz uaktywnia także szlaki sygnałowe przeżycia komórki, co pozwala komórkom nowotworowym pokonać cytotoksyczność wywołaną promieniowaniem. Uważna ocena międzybłoniaka na poziomie biologicznym, z naciskiem na mechanizmy działania szlaków sygnałowych prowadzących komórkę na drogę przeżycia, może być pomocna przy wyborze opcji terapeutycznej. Niniejsza praca skupia się na dostępnych metodach leczenia złośliwego międzybłoniaka opłucnej, nowym podejściu terapeutycznym opartym na najnowszych badaniach, wykorzystującym inhibitory ukierunkowane na różne szlaki sprzyjające przeżyciu i radioterapii stosowanej w celu optymalizacji metod leczenia