Daratumumab for the treatment of multiple myeloma

Goldsmith, Scott; Foley, Nicole; Schroeder, Mark A.

doi:10.1358/dot.2021.57.10.3313853

Cited by 17 publications

(14 citation statements)

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“…Multiple myeloma (MM), which arises from the uncontrolled proliferation of malignant plasma cells, is the second most common hematological malignancy (1). The overall survival (OS) of MM patients has been significantly increased due to the availability of drugs such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies, and transplantation of autologous stem cells (2)(3)(4). However, MM is still incurable, and almost all patients will suffer from disease recurrence (5).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, increasing evidence showed that INPP4B is a negative regulator of the PI3K/Akt signaling pathway in many cancers (14). INPP4B inhibited PI3K/Akt signaling pathway suppresses PI3K/Akt signaling by converting PI (3,4)P(2) to PI(3)P (15,16). Furthermore, loss of INPP4B protein expression in breast and ovarian cancer is associated with decreased patient survival (17).…”

Section: Introductionmentioning

confidence: 99%

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Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

Chen

Gao

et al. 2022

Front. Oncol.

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Inositol polyphosphate-4-phosphatase type II (INPP4B) has been identified as a tumor suppressor, while little is known about its expression and function in multiple myeloma (MM). In this study, we evaluated the expression of INPP4B in 28 cases of newly diagnosed MM patients and 42 cases of extramedullary plasmacytoma (EMP) patients compared with normal plasma cells and found that low INPP4B expression was correlated with poor outcomes in MM patients. Moreover, expression of INPP4B in seven MM cell lines was all lower than that in normal plasma cells. In addition, loss of function of INPP4B promoted cell proliferation in MM cells; however, gain of function suppressed MM cells proliferation and arrested the cell cycle at G0/G1 phage. Meanwhile, knockdown of INPP4B enhanced resistance, but overexpression promoted sensitivity to bortezomib treatment in MM cells. Mechanistically, we found that INPP4B exerted its role via inhibiting the phosphorylation of Akt at lysine 473 but not threonine 308, which attenuated the activation of the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Therefore, we identified an inhibitory effect of INPP4B in MM, and our findings suggested that loss of INPP4B expression is a risk factor of aggressive MM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

Chen

Gao

et al. 2022

Front. Oncol.

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“…The so-called checkpoint inhibitors, such as the anti-CTLA4 antibody ipilimumab [ 84 ] or the anti-programmed death-1 (PD-1) antibodies nivolumab and pembrolizumab [ 85 ], mostly target exhausted autologous T cells, although NK cells can also express PD-1 [ 83 ]. Furthermore, the anti-CD20 antibody rituximab (against malignant B cell neoplasms) [ 86 ], as well as the anti-CD38 antibody daratumumab [ 87 ] and the anti-CD319 (SLAMF7) antibody elotuzumab [ 88 ], which are both part of the treatment arsenal against multiple myeloma, bind to the AR CD16 via their constant Fc portion and to the tumor cells by their variable part specific for the cited tumor antigens. In addition, elotuzumab is also able to activate NK cells through the binding to SLAMF7 expressed by NK cells and thus acts both in a CD16-dependent and -independent manner [ 88 ].…”

Section: Harnessing Of Autologous Nk Cellsmentioning

confidence: 99%

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

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“…For relapsed/refractory patients, a variety of new drugs such as panobinostat, carfilzomib, elotuzumab, daratumumab, and ixazomib may be applied [61]. Daratumumab can offer excellent results for patients over 65 years [62].…”

Section: Multiple Myelomamentioning

confidence: 99%

Anemia of geriatric patients

Gadó

Khodier

Virág

et al. 2022

PhysInt

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Anemia is a common finding in the elderly. Approximately 10 percent of the elderly suffers from anemia. Anemia per se is an independent factor of mortality in older patients regardless its cause. Frailty is also frequent in geriatric patients. That means that there is a decreased reserve capacity to react to different stress factors including anemia. The frequent presence of heart failure and also impaired cerebrovascular circulation makes more difficult to tolerate anemia in older age. Anemia is a symptom, finding and treating the underlying cause is also important. Treatment always depends on clinical findings: the more severe the symptoms, the more important to treat them. Severity of anemia depends not only the underlying cause, degree of anemia, co-morbidities and frailty of the patients, but also the speed of its development. Sudden blood loss due to an accident is less well tolerated than the same degree of anemia due to B12 deficiency. Main causes of anemia in the elderly include nutritional deficiencies, chronic diseases, tumors, and certain hematological malignancies such as chronic lymphocytic leukemia, multiple myeloma, myelodysplastic syndrome.

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Daratumumab for the treatment of multiple myeloma

Cited by 17 publications

References 0 publications

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Anemia of geriatric patients

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