egfr inhibitor br Drug resistance In clinical
Drug resistance In clinical practice, there is no cross–drug-resistance between As2O3 and RA or other antileukemic agents. This may be explained by the non-liposoluble nature of As2O3, its small molecular weight, and its distinctive modes of action . In our observation, primary As2O3 resistance was found in 35.9% of refractory patients, 15.3% of patients whose disease relapsed after nonarsenic induction and consolidation, and in 5.7% of newly diagnosed APL patients; the rate of acquired resistance to As2O3 was 26.7% (23/86). In the latter instance, an increased dose of As2O3 enabled more than half of resistant patients to regain CR, presumably through overcoming an “inertia” in arsenic receptor or signaling pathways . Geng et al.  found cross–drug-resistance between As2O3 and cisplatin. An increased As2O3 dose or action time resulted in a decrease of multidrug resistance protein egfr inhibitor and reversed the resistance.
Toxicity and side effects
As2O3 treatment was recently proposed as an alternative therapy for APL, because it can induce CR in patients with either RA-sensitive or RA-resistant APL. Intriguingly, As2O3 was also induced degradation of PML/RARα chimeras and to reorganize PML nuclear bodies（PML-NBs） . In APL patients, RA triggers differentiation, whereas As2O3 induces both a partial differentiation and apoptosis. Although their mechanisms of action are believed to be distinct, both drugs induce catabolism of the oncogenic PML/RARα-fusion protein. Although APL cell lines resistant to one of these agents are sensitive to the other, the benefit of combining RA and arsenic in cell culture remains controversial. Shao et al.  believe that As2O3 and RA inhibit each other，s therapeutic effects. Lallemand et al.  used syngeneic grafts of leukemic blasts from PML/RARα transgenic rats as a model for APL to establish that RA and As2O3 act synergistically in vivo, and encouraged using this combination for APL patients. This exemplifies how murine models of human leukemia can be used to design or optimize therapies. RA and As2O3 together also prolonged the survival of recipients mare than did either drug alone. In contrast, neither in promyelocytic zinc finger protein (PLZF)-RARα transgenic rats nor in nude rats that received transplanted of PML/RARα cells did any of the 3 regimens induce CR . However, in a clinical trial, RA combined with As2O3 for de novo APL treatment, achieved CR in 29/31 (93.5%) patients. The PML/RARα-fusion gene that was positive in all 29 patients before treatment turned negative in only 3 of them (10.3%) by the time of CR, and 10/13 patients (76.9%) who were PML/RARα positive became negative after the consolidation treatment. However, the results were not significant compared with those for As2O3 and RA usage or chemotherapy at a single dosage to treat APL . In the author，s clinical practice, single-agent As2O3 or RA administration, rather than the combination, is used for induction therapy in newly diagnosed APL cases to prevent a possible aggravation of APLDS, or other adverse events. Nevertheless, As2O3 and RA in combination has been adopted in some instances involving refractory or resistant disease or multiple relapses. Clearly, both drugs are highly effective; they do not cause cross–drug-resistance, and they share the same principal mode of action, specifically the induction of differentiation .
Conflict of interest
Introduction Tyrosine kinase inhibitors (TKIs) such as imatinib (IM) can dramatically improve the prognosis of patients with chronic myeloid leukemia (CML), and some patients showing a deep molecular response (DMR) can attempt to discontinue IM treatment.  However, Richter et al. previously reported that musculoskeletal pain can occur in association with the withdrawal of IM.  In a previous imatinib suspension and validation (ISAV) study, analysis of the quality of life showed a trend towards increased pain score following the cessation of IM . Furthermore, Lee et al. showed that 30% of patients who discontinued IM developed musculoskeletal pain or pruritus in the Korean Imatinib Discontinuation (KID) study .