Impact of prior cancer history on survival in brain malignancy: A propensity score-adjusted, population-based study.

BACKGROUND: Individuals with a Prior Cancer History (PCH) are often excluded from clinical trials. However, a growing body of evidence suggests that prior cancer history does not present adverse outcomes on cancer patients. The evidence on the survival of brain cancer patients in this regard remains widely unknown. METHODS: We conducted a retrospective cohort study to estimate the prevalence and impact of prior cancer on survival of patients diagnosed with brain cancer. Data of patients who were diagnosed with brain cancer as their first or second primary malignancy between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to ensure comparable baseline characteristics among the patients. Survival analysis was conducted using the Kaplan-Meier method, as well as multivariate Cox proportional hazard and multivariate competing risk models. RESULTS: Out of 42 726 patients, 1189 (2.78%) had PCH. Genitourinary (40.4%), Breast (13.6%), Hematologic and Lymphatic (11.4%), and Gastrointestinal malignancies (11.3%) were the most common types of prior cancer. PCH served as a significant risk factor for Overall Survival (OS) (Adjusted Hazard Ratio [AHR] 1.26; 95% CI [1.15-1.39]; p < .001) but did not have a statistically significant impact on Brain Cancer-Specific Survival (BCSS) (AHR 0.97; 95% CI [0.88-1.07]; p = .54). Glioblastoma exhibited the most substantial and statistically significant impact on survival as compared to other histological types. Of all the organs systems, only prior Gastrointestinal and Hematologic and Lymphatic malignancies had a statistically significant impact on OS of patients. CONCLUSION: Our findings indicate that PCH does not exert a substantial impact on the survival of brain cancer patients, except in cases involving gastrointestinal or hematologic and lymphatic PCH, or when the brain cancer is glioblastoma.

Waldenström macroglobulinemia: a review of pathogenesis, current treatment, and future prospects.

Waldenström macroglobulinemia (WM) is a chronic B-cell lymphoproliferative disorder characterized by lymphoplasmacytic cell overgrowth in the bone marrow and increased secretion of IgM immunoglobulins into the serum. Patients with WM have a variety of clinical outcomes, including long-term survival but inevitable recurrence. Recent advances in disease knowledge, including molecular and genetic principles with the discovery of MYD88 and CXCR4 mutations, have rapidly increased patient-tolerable treatment options. WM patients may benefit from chemotherapy regimens that include rituximab-based regimens, alkylating drugs, proteasome inhibitors, monoclonal antibodies, and drugs targeting Bruton tyrosine kinase inhibitors. In light of these advancements, patients can now receive treatment customized to their specific clinical characteristics, focusing on enhancing the depth and durability of their response while limiting the adverse effects. Despite the rapidly developing therapeutic armament against WM, a lack of high-quality evidence from extensive phase 3 trials remains a significant challenge in the research. We believe clinical outcomes will keep improving when new medicines are introduced while preserving efficacy and minimizing toxicity.

Pneumocystis jiroveci Pneumonia: A Review of Management in Human Immunodeficiency Virus (HIV) and Non-HIV Immunocompromised Patients.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in Pneumocystis jirovecii pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of Pneumocystis jirovecii pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for Pneumocystis jirovecii pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.

Total Body Irradiation Versus Chemotherapy Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.

Allogeneic hematopoietic stem cell transplant (HSCT) is indicated in pediatric patients with acute lymphoblastic leukemia (ALL) who have relapsed or are at a very high risk of relapse during first complete remission. Two types of myeloablative conditioning are employed before allogeneic HSCT: total body irradiation (TBI)-based regimens and chemotherapy (CHT) alone. This study compares the efficacy and safety of TBI-based regimens and CHT-based conditioning in pediatric, adolescent, and young adult patients with ALL (0-24 years old). TBI-based and CHT-conditioning regimens were evaluated in 4262 and 1367 patients, respectively, from 15 studies. Compared to CHT alone, TBI-based regimens were associated with better overall survival (OS), relative risk (RR) 1.21, better event-free survival (RR 1.34), and a reduced risk of relapse (RR 0.69). Both approaches had comparable risk of acute graft-versus-host disease (GVHD), grades 3 to 4 acute GVHD, chronic GVHD, and nonrelapse mortality (NRM). In the subgroup analysis for patients in first complete remission, TBI-based regimens and CHT alone had comparable OS and NRM. Our results demonstrate the superiority of TBI-based regimens compared to CHT alone in pediatric patients with ALL.

Efficacy of Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Catheter ablation (CA) has emerged as an effective therapy for AF. We conducted a meta-analysis to update the current clinical evidence on the efficacy of CA for AF in patients with HCM. We searched PubMed, Embase, Cochrane and Clinicaltrials.gov for interventional and observational studies assessing single and multiple procedure success rate of CA in HCM patients. Our meta-analysis included 25 studies involving 1817 patients. Success rate following single procedure was 40.4% (95% CI 33.1 to 48.0%) at latest follow-up. The pooled success rate following multiple procedures was 51.4% (95% CI 42.9% to 60.0%) at latest follow-up. In the subgroup analysis for AF subtype, TCA was more successful for paroxysmal AF compared to non-paroxysmal AF. For the subset of studies reporting drug-free success rate, single and multiple procedures had a success rate of 33.4% (95% CI 19.3 to 49.1%) and 51.8% (95% CI 41.3 to 62.2%) at latest follow-up, respectively. CA is a suitable option for AF in patients with HCM. Success rate is greater in paroxysmal AF, after multiple procedures and with antiarrhythmic drugs.

Development and Characterization of Zein/Ag-Sr Doped Mesoporous Bioactive Glass Nanoparticles Coatings for Biomedical Applications.

Implants are used to replace damaged biological structures in human body. Although stainless steel (SS) is a well-known implant material, corrosion of SS implants leads to the release of toxic metallic ions, which produce harmful effects in human body. To prevent material degradation and its harmful repercussions, these implanted materials are subjected to biocompatible coatings. Polymeric coatings play a vital role in enhancing the mechanical and biological integrity of the implanted devices. Zein is a natural protein extracted from corn and is known to have good biocompatibility and biodegradability. In this study, zein/Ag-Sr doped mesoporous bioactive glass nanoparticles (Ag-Sr MBGNs) were deposited on SS substrates via electrophoretic deposition (EPD) at different parameters. Ag and Sr ions were added to impart antibacterial and osteogenic properties to the coatings, respectively. In order to examine the surface morphology of coatings, optical microscopy and scanning electron microscopy (SEM) were performed. To analyze mechanical strength, a pencil scratch test, bend test, and corrosion and wear tests were conducted on zein/Ag-Sr doped MBGN coatings. The results show good adhesion strength, wettability, corrosion, and wear resistance for zein/Ag-Sr doped MBGN coatings as compared to bare SS substrate. Thus, good mechanical and biological properties were observed for zein/Ag-Sr doped MBGN coatings. Results suggested these zein/Ag-Sr MBGNs coatings have great potential in bone regeneration applications.

Management of Cervix Atresia with Hematometra by "Genitoscopic Ultrasound-Guided Cervix Fenestration and Balloon Dilatation": A Novel Approach.

Introduction: Cervix atresia causing hematometra usually presents at puberty with cyclic abdominal pain. The management depends upon the type and severity of cervix atresia. We present a novel technique of managing a case of cervix atresia in a 13 years old girl. Case report: A 13 years old girl presented with severe cyclic abdominal pain. Examination revealed normal external genitalia with a palpable tender mass in the suprapubic area. Ultrasonography and MRI suggested a large hematometra with a 1.5 cm long cervix atresia. Vaginoscopy performed under anesthesia showed a normal-looking vagina and a blind cervix. During vaginoscopy and dynamic ultrasound (US) guidance, a spinal needle was passed through the vagina and center of the atretic cervix into the uterine cavity containing the hemolyzed blood. Aspiration of the hemolyzed blood and US visualization confirmed the location of the needle in the uterine cavity. A three-stage (esophageal) balloon dilator was passed over a guidewire through the atretic area. The balloon dilator was dilated up to 10 mm using pressure-controlled dilatation. A satisfactory dilatation was achieved, and all the retained hemolyzed blood was drained through the newly created channel. A size 24 Foleys catheter was retained in the uterine cavity and removed after 1 week. A repeat ultranography before subsequent periods showed a recurrent collection and obliteration of the cervix. US-guided balloon dilatations were repeated. A third dilatation was required after an interval of few months. The child remained well after the third dilatation, having regular periods, and is symptom free at 8 months follow-up, however, may need more sessions of cervix dilatations. Conclusion: Genitoscopic US-guided cervix fenestration and balloon dilatation is an effective technique for treatment of cervix atresia. It is a safe technique, avoids major surgical reconstructions, is a minimally invasive procedure, and can be used in selected cases of cervix atresia.

Prognostic Impact of Red Cell Distribution Width on the Development of Contrast-Induced Nephropathy, Major Adverse Cardiac Events, and Mortality in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention.

Red cell distribution width (RDW) serves as an independent predictor towards the prognosis of coronary artery disease (CAD) in patients undergoing percutaneous coronary intervention (PCI). A systematic search of databases such as PubMed, Embase, Web of Science, and Cochrane library was performed on October 10th, 2019, to elaborate the relationship between RDW and in hospital and long term follow up, all-cause and cardiovascular mortality, major adverse cardiac events (MACE) and development of contrast-induced nephropathy (CIN) in patients with CAD undergoing PCI. Twenty-one studies qualified this strict selection criterion (number of patients = 56,425): one study was prospective, and the rest were retrospective cohorts. Our analysis showed that patients undergoing PCI with high RDW had a significantly higher risk of in-hospital all-cause mortality (OR 2.41), long-term all-cause mortality (OR 2.44), cardiac mortality (OR 2.65), MACE (OR: 2.16), and odds of developing CIN (OR: 1.42) when compared to the patients with low RDW. Therefore, incorporating RDW in the predictive models for the development of CIN, MACE, and mortality can help in triage to improve the outcomes in coronary artery disease patients who undergo PCI.

Pheochromocytoma: An Incidental Finding in an Asymptomatic Older Adult With Renal Oncocytoma.

A high index of suspicion for pheochromocytoma is necessary during the workup of secondary hypertension as untreated pheochromocytoma may lead to significant morbidity and mortality, especially in patients who require any surgical treatment.

Role and mechanism of autophagy-regulating factors in tumorigenesis and drug resistance.

A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.

Fundamentals of Light Chain Cardiac Amyloidosis: A Focused Review.

The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement, including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis. The purpose of this manuscript is to review the advances in the diagnosis and management of cardiac amyloidosis with the aim of educating colleagues who provide care in the primary care setting. We have summarized the pathogenesis of amyloidosis, its association with plasma cell dyscrasias, novel diagnostic and surveillance approaches including echocardiography, cardiovascular magnetic resonance imaging, histopathologic techniques, systemic biomarkers, and advanced treatment approaches including supportive symptomatic management and standard of care chemotherapy targeting the amyloid deposits. Given the overall poor prognosis of amyloidosis, we have also discussed the role of palliative and hospice care.

Echocardiographic parameters associated with recovery in heart failure with reduced ejection fraction.

OBJECTIVE: The study aims to determine the clinical and echocardiographic parameters of patients with recovered heart failure (HFrecEF). METHODOLOGY: Sixty-seven patients (cases) were identified as heart failure with recovered ejection fraction (HFrecEF), defined as improvement in EF ≥ 10%. Sixty-nine patients (controls) were randomly selected by convenience sampling with no or <10% improvement in EF (HFrEF non-recovered). RESULTS: The mean interval between baseline and follow-up echocardiography was 10.5 months in cases and 11.2 months in the control group. HFrecEF showed a 22.7% improvement in mean ejection fraction, and HFrEF non-recovered group also showed a minor increment of 5.5%. HFrecEF patients were significantly younger (49.51 vs 57.54 years, P .001) with non-ischemic cardiomyopathy (86.6% vs 52.2%). Patients with HFrecEF had significantly less left ventricular end-diastolic and end-systolic volumes (LVEDV: 162.51 mL vs 208.54 mL, P < .001; LVESV: 119.81 mL vs 157.13 mL, P < .001) and index left atrial volume (37.66 mL vs 47.09 mL, P < .001) than patients with non-recovered EF. The right ventricle (RV) and inferior vena cava were significantly dilated with higher mean tricuspid annular plane systolic excursion (TAPSE) among patients with HFrecEF than HFrEF non-recovered. CONCLUSION: Based on univariate analysis, younger age, non-ischemic etiology, LVEDV, LVESV, deceleration time, better TAPSE, dilated right ventricle, dilated IVC, and smaller left atrial volumes were found significant, but on multivariate logistic regression model only left ventricle end-diastolic volume, left atrial volume, and TAPSE were linked to the recovery of ejection fraction.

Frequency- and Power-Dependent Photoresponse of a Perovskite Photodetector Down to the Single-Photon Level.

Organometallic halide perovskites attract strong interests for their high photoresponsivity and solar cell efficiency. However, there was no systematic study of their power- and frequency-dependent photoresponsivity. We identified two different power-dependent photoresponse types in methylammonium lead iodide perovskite (MAPbI3) photodetectors. In the first type, the photoresponse remains constant from 5 Hz to 800 MHz. In the second type, absorption of a single photon can generate a persistent photoconductivity of 30 pA under an applied electric field of 2.5 × 104 V/cm. Additional absorbed photons, up to 8, linearly increase the persistent photoconductivity, which saturates with the absorption of more than 10 photons. This is different than single-photon avalanche detectors (SPADs) because the single-photon response is persistent as long as the device is under bias, providing unique opportunities for novel electronic and photonic devices such as analogue memories for neuromorphic computing. We propose an avalanche-like process for iodine ions and estimate that absorption of a single 0.38 aJ photon triggers the motion of 108-9 ions, resulting in accumulations of ions and charged vacancies at the MAPbI3/electrode interfaces to cause the band bending and change of electric material properties. We have made the first observation that single-digit photon absorption can alter the macroscopic electric and optoelectronic properties of a perovskite thin film.

Assessment of forest cover and carbon stock changes in sub-tropical pine forest of Azad Jammu & Kashmir (AJK), Pakistan using multi-temporal Landsat satellite data and field inventory.

This study aimed at estimating temporal (1989-2018) change in forest cover, carbon stock and trend in corresponding CO2 emissions/sequestration of a sub-tropical pine forest (STPF) in AJK, Pakistan. Our field inventory estimation shows an average above ground biomass (AAGB) accumulation of 0.145 Kt/ha with average carbon stock (ACS) value of 0.072 Kt/ha. Landsat TM, ETM+ and OLI images of 1989, 1993, 1999, 2005, 2010, 2015 and 2018 were used to extract vegetation fractions through Linear Spectral Mixture Analysis (LSMA) and forest area was calculated for respective years. Based on the forest area and estimated ACS value, the biomass carbon stock with corresponding CO2 emissions/sequestration was worked out for each time and change in forest carbon stock was determined for different time periods from 1989 to 2018. Our analysis shows net increase of 561 ha in forest cover and 40.39 Kt of ACS along with increase in corresponding CO2 sequestrations of 147.83 Kt over the study period. The results based on combination of remote sensing and field inventory provide valuable information and scientific basis to plan and ensure sustainable forest management (SFM) through reforestation, protection and conservation to enhance and maintain adequate forest cover and reduce CO2 emissions.

A Single-Center Experience and Literature Review of Management Strategies for Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Patients.

INTRODUCTION: The aim of our study is to evaluate risk factors associated with the development of C. difficile infection (CDI) in hematopoietic stem cell transplant (HSCT) patients, determine its incidence and report outcomes of CDI in our patient population. METHODS: We performed a retrospective review of medical records of adult HSCT recipients diagnosed between 2013 and 2016 at our center. Logistic regression models were used to determine the relationship between risk factors and the odds of CDI. RESULTS: The overall incidence of CDI in HSCT patients was 9.4%. The incidence of CDI was higher in allogeneic HSCT (20%) versus autologous HSCT (4.8%). No statistically significant differences in age, gender, cancer type, transplant type were found between those who developed CDI and those who did not. However, patients with CDI had a longer length of stay (25 days) and used more antibiotics (30 days prior to and during admission for HSCT) than non-CDI patients (19 days). Only two of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after HSCT. No patient suffered from toxic megacolon or ileus and no patient underwent colectomy. There was no mortality associated with CDI at our center. CONCLUSION: CDI has an incidence rate of 9.4% in HSCT recipients. Established risk factors including age, gender, cancer type, and transplant type were not identified as risk factors in our population. However, longer LOS and use of greater than four lines of antibiotics were observed among those with CDI compared to those without CDI.

Room-temperature long-wave infrared detector with thin double layers of amorphous germanium and amorphous silicon.

A longwave-infrared photodetector made of double layers of 100nm amorphous germanium (a-Ge) and 25nm amorphous silicon (a-Si) have been demonstrated. Under room temperature, the device shows the responsivity of 1.7 A/W, detectivity of 6×108 Jones, and noise equivalent power (NEP) of 5pW/√Hz under 5V bias and at 20kHz operation. Studies of frequency dependent characteristics and device modeling indicate that, above 100Hz or beyond the bandwidth of thermal response, the device operates as a quantum detector having the photoelectrons produced by optical excitation from the bandtail states to the mobile states of a-Ge. The superior device performance may be attributed to the combination of two amplification mechanisms: photoconductive gain in a-Ge and cycling excitation process (CEP) in a-Si, with the latter being the dominant factor. Besides its attractive performance, the device has a simple structure and is easy to fabricate at low cost, thus holding promise for night vision, sensing, autonomous driving, and many other applications.

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development.

BACKGROUND: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with lenalidomide (Len) and dexamethasone (Dex), producing a clinical benefit rate (CBR) of 83%. Additionally, Isa used in combination with pomalidomide (Pom) and Dex resulted in a CBR of 73%. Indatuximab Ravtansine (anti-CD138 antibody-drug conjugate) produced an ORR of 78% and 79% when used in combination with Len-Dex and Pom-Dex, respectively. CONCLUSIONS: Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted.

Does antimicrobial coating and impregnation of urinary catheters prevent catheter-associated urinary tract infection? A review of clinical and preclinical studies.

Introduction: Catheter-associated urinary tract infection (CAUTI) is one of the most common nosocomial infections in hospitals, accounting for 36% of all health care-associated infections. Areas covered: We aimed to address the potential impact of antimicrobial coating of catheter materials for the prevention of CAUTI and to analyze the progress made in this field. We conducted literature searches in the PubMed, Embase, and Cochrane Library databases, and found 578 articles. Data from 60 articles in either the preclinical or clinical stage were analyzed in this expert review. Expert opinion: The literature review revealed many promising methods for preventing CAUTI. Recent studies have suggested the combination of silver-based products and antibiotics, owing to their synergistic effect, to help address the problem of antibiotic resistance. Other coating materials that have been tested include nitric oxide, chlorhexidine, antimicrobial peptides, enzymes, and bacteriophages. Because of heterogeneity among studies, it is difficult to reliably comment on the clinical efficacy of different coating materials. Future research should focus on double-blind randomized clinical trials for evaluating the role of these potential coating agents.

Upper Gastrointestinal Manifestation of Bezoars and the Etiological Factors: A Literature Review.

A gastric bezoar is a compact mass of indigestible foreign materials that accumulate and consolidate in the stomach; however, it can be found in other sites of the gastrointestinal tract. The causative manner of this condition is complex and multifactorial. The main purpose of the review was to raise awareness among clinicians, particularly gastroenterologists, that patients with certain risk factors or comorbid conditions are predisposed to gastric bezoar formation. Early diagnosis and prompt intervention are crucial to avoid bezoar-induced complications. Upper gastrointestinal endoscopy is the standard diagnostic and therapeutic method for gastric bezoars. However, for large size bezoars, surgical intervention is needed.

Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma.

Multiple myeloma (MM) is a genetically complex disease. Identification of mutations and aberrant signaling pathways that contribute to the progression of MM and drug resistance has potential to lead to specific targets and personalized treatment. Aberrant signal pathways include RAS pathway activation due to RAS or BRAF mutations (targeted by vemurafenib alone or combined with cobimetinib), BCL-2 overexpression in t(11:14) (targeted by venetoclax), JAK2 pathway activation (targeted by ruxolitinib), NF-κB pathway activation (treated with DANFIN combined with bortezomib), MDM2 overexpression, and PI3K/mTOR pathway activation (targeted by BEZ235). Cyclin D1 (CCND1) and MYC are also emerging as key potential targets. In addition, histone deacetylase inhibitors are already in use for the treatment of MM in combination therapy, and targeted inhibition of FGFR3 (AZD4547) is effective in myeloma cells with t(4;14) translocation. Bromodomain and extra terminal (BET) protein antagonists decrease the expression of MYC and have displayed promising antimyeloma activity. A better understanding of the alterations in signaling pathways that promote MM progression will further inform the development of precision therapy for patients.