Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imatinib is a selective tyrosine kinase inhibitor which acts on breakpoint cluster region-Abelson fusion gene (BCR-ABL) positive leukemia including all phases of chronic myeloid leukemia and acute lymphoblastic leukemia. It may induce rapid apoptosis and subsequent tumor lysis syndrome. Only 3 cases of imatinib-induced tumor lysis syndrome have been reported. We herein described an additional patient with BCR-ABL (ela2) positive acute lymphoblastic leukemia who developed tumor lysis syndrome after 10-day treatment with imatinib. Experience in the current case suggests that preventive measures for tumor lysis syndrome, including allopurinol and hydration, should be taken for patients with high leukemia burden who receive imatinib therapy, and parameters of tumor lysis should be monitored in the early phase of therapy.
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PMID:Imatinib-induced tumor lysis syndrome: report of a case and review of the literature. 1909 99

The electrolyte imbalance in advanced cancer patients, including hyperkalemia, hypercalcemia and hyponatremia, can be induced by various factors. Hyperkalemia is occasionally induced by chemotherapy for very large malignant tumors, due to tumor lysis syndrome. Hypercalcemia and hyponatremia are often observed in patients with breast cancer, renal cancer, prostate cancer, and the like, as a paraneoplastic syndrome. Some part of hypercalcemia results from osteolysis, but the majority is induced by hormonal factors, such as parathyroid hormone-related protein. One of the paraneoplastic causes of hyponatremia is antidiuretic hormone-producing tumor. These disorders could be morbid or even motile, resulting from encephalopathy or arrhythmia in some cases. However, it should be kept in mind that they could be improved or cured by prompt treatment. Recently, after approval of the molecular targeted drugs for epidermal growth factor receptors, such as cetuximab and panitumumab, the incidence of hypomagnesia with use of these monoclonal antibodies, is relatively frequent. In addition, small molecular targeted drugs, such as m-TORinhibitors and ABL kinase inhibitors, also exert adverse reactions including hypomagnesia and hypophosphatemia. Careful monitoring of the serum concentration of magnesium and phosphate ions, to which little attention was paid previously, is a key issue in these cases.
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PMID:[Cancer and electrolytes imbalance]. 2056 1

Mantle cell lymphoma accounts for 5-7% of all non-Hodgkin's lymphomas. Under the current WHO classification, it is categorized as an indolent B cell lymphoma, but has an aggressive clinical course. New insights into leukemogenic molecular pathways of mantle cell lymphoma have uncovered unique therapeutic targets. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is the newest drug in the arsenal that has shown promising efficacy in relapsed mantle cell lymphoma. Long-term studies have shown that grade 3 or 4 adverse events are infrequent. Asymptomatic lymphocytosis is frequently seen with ibrutinib use in mantle cell lymphoma; however, tumor lysis syndrome is an extremely rare complication. To date, only two patients with ibrutinib-associated tumor lysis syndrome in mantle cell lymphoma have been described in a long-term follow-up study. Both patients met laboratory criteria for tumor lysis syndrome, however, but did not develop clinical tumor lysis syndrome. We, here describe a patient with relapsed mantle cell lymphoma who developed clinical tumor lysis syndrome with ibrutinib monotherapy.
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PMID:Ibrutinib-associated tumor lysis syndrome in a patient with mantle cell lymphoma: A case report. 2697 May 73

The development of tumor lysis syndrome (TLS) in association with treatment for myeloproliferative neoplasms (MPNs) is relatively rare. We herein present the case of a post-polycythemia vera (PV) myelofibrosis patient with massive splenomegaly who developed laboratory TLS after treatment with ruxolitinib, a potent JAK1/JAK2 inhibitor. She also exhibited a rapid reduction of spleen volume. Our present case suggests the potential risk of TLS development after ruxolitinib treatment, particularly in patients with massive splenomegaly.
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PMID:Tumor Lysis Syndrome after the Administration of Ruxolitinib in a Patient with Post-polycythemia Vera Myelofibrosis. 2879 80

Targeted therapies including the engineered afucosylated anti-CD20 monoclonal antibody obinutuzumab, Bruton's tyrosine kinase inhibitor ibrutinib, and B-cell lymphoma protein 2 inhibitor venetoclax have demonstrated significant clinical activity in chronic lymphocytic leukemia (CLL) and, based on their complementary mechanisms, are ideal for combination. However, combining venetoclax with other active agents raises safety concerns, as it may increase the risk for tumor lysis syndrome. To minimize this risk, we designed and implemented a fixed-duration regimen using sequentially administered obinutuzumab followed by ibrutinib (cycle 2) and venetoclax (cycle 3), for a total of fourteen 28-day cycles. This phase 1b study included 12 patients with relapsed or refractory CLL. We tested 3 dose levels of venetoclax and identified the doses of all 3 agents approved by the US Food and Drug Administration for use in the combination. Adverse events were consistent with known toxicities of the individual agents, with hematologic adverse events being most frequent. No clinically significant tumor lysis syndrome occurred. The overall response rate was 92% (95% confidence interval, 62%-100%), with 42% (5/12) achieving a complete remission or complete remission with incomplete marrow recovery. There were 6 patients with no detectable CLL in both the blood and bone marrow at the end of treatment. We found this regimen to be safe and tolerable in CLL, and capable of inducing deep responses, justifying future study in our ongoing phase 2 cohorts of relapsed or refractory and treatment-naive patients, as well as larger phase 3 trials currently in planning. This trial was registered at www.clinicaltrials.gov as #NCT02427451.
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PMID:Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia. 3030 74

Advances in the molecular biology of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and development of molecularly targeted therapies have resulted in treatment innovations. Therapeutic approaches for previously untreated CLL/SLL patients are changing from chemoimmunotherapy (CIT) to molecularly targeted drugs. The aim of therapy for CLL patients has been to control the disease; however, FCR (fludarabine, cyclophosphamide, rituximab) has improved outcomes and reduced the high incidence of undetectable minimum/measurable residual disease (MRD) in previously untreated CLL patients with no 17p deletion/TP53 disruption and mutated immunoglobulin heavy chain gene (IGHV). Patients achieving undetectable MRD in the bone marrow are expected to be cured. BTK inhibitors and BCL-2 inhibitors are effective for CLL/SLL patients. However, atrial fibrillation and bleeding are associated with the BTK inhibitor, ibrutinib, while tumor lysis syndrome is an adverse event (AE) of the BCL-2 inhibitor, venetoclax. Although these novel targeted drugs are very useful, they are also expensive. Emergence of resistant clones of CLL cells must also be addressed. Therefore, treatments of indefinite duration until progression have been replaced by fixed-duration treatments. This review introduces advances in the treatment of previously untreated CLL/SLL patients in Europe and the United States.
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PMID:Evolution in the management of chronic lymphocytic leukemia in Japan: should MRD negativity be the goal? 3225 66