Promoting Linguistically Based Health Literacy in Doctors for Better Cancer Healthcare in Cyprus.

This paper explores a novel approach in cancer healthcare, underscoring the significance of fostering health literacy among doctors by enhancing their ability to employ linguistically oriented strategies to extract and interpret the linguistic behavior of patients. The focus is on the Greek-Cypriot context, where research on health literacy is still in its nascent stages.

Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer.

PURPOSE: The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor-positive (ER+), HER2- breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women. EXPERIMENTAL DESIGN: Tumor samples from 385 pre-menopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence-free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18-1.50; P = 7.2 × 10-6; HR, 3.58; 95% CI, 2.26-5.66; P = 9.8 × 10-8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40-15.17; P = 4.2 × 10-3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%-99%) and 76% (95% CI, 67%-82%), respectively. CONCLUSIONS: The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.

GSK3ß and mTORC1 Represent 2 Distinct Signaling Markers in Peripheral Blood Mononuclear Cells of Drug-Naive, First Episode of Psychosis Patients.

BACKGROUND AND HYPOTHESIS: Schizophrenia is characterized by a complex interplay between genetic and environmental risk factors converging on prominent signaling pathways that orchestrate brain development. The Akt/GSK3ß/mTORC1 pathway has long been recognized as a point of convergence and etiological mechanism, but despite evidence suggesting its hypofunction, it is still not clear if this is already established during the first episode of psychosis (FEP). STUDY DESIGN: Here, we performed a systematic phosphorylation analysis of Akt, GSK3ß, and S6, a mTORC1 downstream target, in fresh peripheral blood mononuclear cells from drug-naive FEP patients and control subjects. STUDY RESULTS: Our results suggest 2 distinct signaling endophenotypes in FEP patients. GSK3ß hypofunction exhibits a promiscuous association with psychopathology, and it is normalized after treatment, whereas mTORC1 hypofunction represents a stable state. CONCLUSIONS: Our study provides novel insight on the peripheral hypofunction of the Akt/GSK3ß/mTORC1 pathway and highlights mTORC1 activity as a prominent integrator of altered peripheral immune and metabolic states in FEP patients.

Adiponectin, leptin and resistin levels in first-episode, drug-naïve patients with psychosis before and after short-term antipsychotic treatment.

OBJECTIVE: There is increasing evidence that adiponectin, resistin and leptin may be implicated in the pathophysiology of neuropsychiatric disorders, including schizophrenia. The results of the studies so far remain controversial. Our aim was to compare serum adiponectin, leptin and resistin levels between drug-naïve, first -episode patients with psychosis and healthy controls and in the same group of patients after six weeks of antipsychotic treatment. METHODS: Forty first-episode patients with psychosis and 40 matched controls were included in the study. Serum levels of adiponectin, resistin and leptin were measured by enzyme linked immunosorbent assay (ELISA) in both groups. In the patient group, the same adipokines were also measured six weeks after the initiation of antipsychotic treatment. RESULTS: Log-transformed serum levels of adiponectin (mean difference = 1.68, 95% confidence interval [CI] = 1.30 to 2.06, U = 157, p < 0.0001), resistin (0.48, 95% CI = 0.36 to 0.59, t = 8.00, p < 0.0001) and leptin (0.66, 95% CI = 0.52 to 0.80, U = 160, p < 0.0001) were significantly higher to the patient group compared to controls. Leptin levels were significantly decreased in the patient group six weeks after the initiation of antipsychotic treatment (mean change = -0.40, 95% CI = -0.59 to -0.21, W = 666; p < 0.0001) while those of adiponectin and resistin levels did not change significantly. CONCLUSION: In our study we found higher levels of adiponectin, leptin and resistin in drug-naïve, first-episode patients with normal Body Mass Index (BMI) compared to controls. After six weeks of antipsychotic treatment, there was no change in adiponectin and resistin levels, while leptin levels were reduced compared to baseline.

Bochdalek hernia with intrathoracic spleen treated by robotic-assisted mesh repair utilizing indocyanine green contrast media intraoperatively. A case report.

Bochdalek hernias are usually diagnosed in newborns. However, they can occur in adults. Few reports exist regarding robotic repair of such hernias. We present a case of a female patient with symptomatic Bochdalek hernia, including the spleen. Patient was successfully treated by robotic-assisted surgical mesh with the use of indocyanine green (ICG). An 80-year-old female patient presented with dyspnea, angina and intermittent abdominal pain. She had loss of appetite and 15-kg weight loss within 3 months. Past medical history was unremarkable. Imaging revealed a left Bochdalek hernia. The patient underwent robotic-assisted surgery; hernia contents included stomach, parts of colon, omentum and remarkably the spleen. Sac was dissected free. Patency of organs was assessed with ICG. Diaphragmatic defect was repaired with mesh. Bochdalek hernias should be surgically repaired. Minimally invasive therapy is safe and effective. Intraoperative ICG use can provide excellent results with favorable clinical outcomes.

ANANSE: an enhancer network-based computational approach for predicting key transcription factors in cell fate determination.

Proper cell fate determination is largely orchestrated by complex gene regulatory networks centered around transcription factors. However, experimental elucidation of key transcription factors that drive cellular identity is currently often intractable. Here, we present ANANSE (ANalysis Algorithm for Networks Specified by Enhancers), a network-based method that exploits enhancer-encoded regulatory information to identify the key transcription factors in cell fate determination. As cell type-specific transcription factors predominantly bind to enhancers, we use regulatory networks based on enhancer properties to prioritize transcription factors. First, we predict genome-wide binding profiles of transcription factors in various cell types using enhancer activity and transcription factor binding motifs. Subsequently, applying these inferred binding profiles, we construct cell type-specific gene regulatory networks, and then predict key transcription factors controlling cell fate transitions using differential networks between cell types. This method outperforms existing approaches in correctly predicting major transcription factors previously identified to be sufficient for trans-differentiation. Finally, we apply ANANSE to define an atlas of key transcription factors in 18 normal human tissues. In conclusion, we present a ready-to-implement computational tool for efficient prediction of transcription factors in cell fate determination and to study transcription factor-mediated regulatory mechanisms. ANANSE is freely available at https://github.com/vanheeringen-lab/ANANSE.

Cardiac-sparing radiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: We have carried out a study to determine the scope for reducing heart doses in photon beam radiotherapy of locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS AND METHODS: Baseline VMAT plans were created for 20 LA-NSCLC patients following the IDEAL-CRT isotoxic protocol, and were re-optimized after adding an objective limiting heart mean dose (MDHeart). Reductions in MDHeart achievable without breaching limits on target coverage or normal tissue irradiation were determined. The process was repeated for objectives limiting the heart volume receiving ≥ 50 Gy (VHeart-50-Gy) and left atrial wall volume receiving ≥ 63 Gy (VLAwall-63-Gy). RESULTS: Following re-optimization, mean MDHeart, VHeart-50-Gy and VLAwall-63-Gy values fell by 4.8 Gy and 2.2% and 2.4% absolute respectively. On the basis of associations observed between survival and cardiac irradiation in an independent dataset, the purposefully-achieved reduction in MDHeart is expected to lead to the largest improvement in overall survival. It also led to useful knock-on reductions in many measures of cardiac irradiation including VHeart-50-Gy and VLAwall-63-Gy, providing some insurance against survival being more strongly related to these measures than to MDHeart. The predicted hazard ratio (HR) for death corresponding to the purposefully-achieved mean reduction in MDHeart was 0.806, according to which a randomized trial would require 1140 patients to test improved survival with 0.05 significance and 80% power. In patients whose baseline MDHeart values exceeded the median value in a published series, the average MDHeart reduction was particularly large, 8.8 Gy. The corresponding predicted HR is potentially testable in trials recruiting 359 patients enriched for greater MDHeart values. CONCLUSIONS: Cardiac irradiation in RT of LA-NSCLC can be reduced substantially. Of the measures studied, reduction of MDHeart led to the greatest predicted increase in survival, and to useful knock-on reductions in other cardiac irradiation measures reported to be associated with survival. Potential improvements in survival can be trialled more efficiently in a population enriched for patients with greater baseline MDHeart levels, for whom larger reductions in heart doses can be achieved.

Outpatient laser treatment of primary pilonidal disease : the PiLaT technique.

BACKGROUND: The aim of the present study was to assess the effectiveness of the minimally invasive technique pilonidal disease laser treatment (PiLaT) in treating primary (non-recurrent) pilonidal disease in an outpatient setting under local anaesthesia. METHODS: A prospective observational study was conducted on consecutive patients suffering from primary pilonidal disease that were treated at Iasi Private Medical Center, Ioannina, Greece, between April 2015 and December 2016, using a 1.470 nm diode laser (BioLitec, Germany) emitting energy through a radial optic fiber that was inserted in the cyst and accompanying sinus tracts. Patients were discharged half an hour after completion of the procedure. Pain scores [visual analogue scale (VAS)], complications and patient satisfaction were assessed. Follow-up lasted 12 months. RESULTS: There were 60 patients, 51 males and 9 females, with a mean age of 22.7 years (range 15-58). Successful treatment (complete epithelization of cyst and tracts) was documented in 55 out of the 60 patients (92% success rate). VAS pain scores were low and no major complications were recorded. Healing was achieved in 25.4 days (range 17-40) and 53.3% of patients were able to return to work the same day (the rest within 3 days). Of the failures, four patients did not heal and one patient recurred after 5 months. All failures were treated successfully with a second laser procedure except for one who denied re-intervention. Overall patient satisfaction reached 98%. CONCLUSIONS: PiLaT seems to be very close to the ideal treatment of pilonidal disease, since it is safe, easy to perform, almost painless and highly effective.

Reply to comment on 'origins of the changing detector response in small megavoltage photon radiation fields'.

Andreo and Benmakhlouf (2017 Phys. Med. Biol. 62 1518-32) have disputed a finding of Scott et al (2012 Phys. Med. Biol. 57 4461-76) that the variation with field-size of the response of small ion chambers and solid-state dosimeters in small megavoltage photon radiation fields can largely be attributed to density. Further evidence for this finding was provided by Fenwick et al (2018 Phys. Med. Biol. 63 125003), but Andreo and Benmakhlouf (2018 Phys. Med. Biol. 63 125003) have now challenged the methodology used in that study. Specifically, Andreo and Benmakhlouf suggest that mass stopping-powers of fictitious materials used in Monte Carlo radiation transport calculations should be adjusted with material density according to the polarization effect, as if the materials were real and created by compressing other real materials. In this reply, we observe that fictitious materials are not real, and therefore their densities, mass stopping-powers and microscopic radiation interaction cross-sections can be freely and independently chosen to provide the clearest answers to the questions being studied. And we note that the key role played by density in small field detector response was further confirmed by our group back in 2013, using fictitious materials in which mass stopping-powers were adjusted with density, as preferred by Andreo and Benmakhlouf, as well as being held fixed, with very similar results being obtained in both circumstances (Underwood et al 2013a Med. Phys. 40 082102).

Origins of the changing detector response in small megavoltage photon radiation fields.

Differences in detector response between measured small fields, f clin, and wider reference fields, f msr , can be overcome by using correction factors [Formula: see text] or by designing detectors with field-size invariant responses. The changing response in small fields is caused by perturbations of the electron fluence within the detector sensitive volume. For solid-state detectors, it has recently been suggested that these perturbations might be caused by the non-water-equivalent effective atomic numbers Z of detector materials, rather than by their non-water-like densities. Using the EGSnrc Monte Carlo code we have analyzed the response of a PTW 60017 diode detector in a 6 MV beam, calculating the [Formula: see text] correction factor from computed doses absorbed by water and by the detector sensitive volume in 0.5 × 0.5 and 4 × 4 cm2 fields. In addition to the 'real' detector, fully modelled according to the manufacturer's blue-prints, we calculated doses and [Formula: see text] factors for a 'Z → water' detector variant in which mass stopping-powers and microscopic interaction coefficients were set to those of water while preserving real material densities, and for a 'density → 1' variant in which densities were set to 1 g cm-3, leaving mass stopping-powers and interaction coefficients at real levels. [Formula: see text] equalled 0.910 ± 0.005 (2 standard deviations) for the real detector, was insignificantly different at 0.912 ± 0.005 for the 'Z → H2O' variant, but equalled 1.012 ± 0.006 for the 'density → 1' variant. For the 60017 diode in a 6 MV beam, then, [Formula: see text] was determined primarily by the detector's density rather than its atomic composition. Further calculations showed this remained the case in a 15 MV beam. Interestingly, the sensitive volume electron fluence was perturbed more by detector atomic composition than by density; however, the density-dependent perturbation varied with field-size, whereas the Z-dependent perturbation was relatively constant, little affecting [Formula: see text].

Spontaneous biloma due to an intrahepatic cholangiocarcinoma: An extremely rare case report with long term survival and literature review.

Cholangiocarcinomas are tumors that arise from the ductal epithelium of the intrahepatic or extra-hepatic bile ducts. Patients are usually asymptomatic or may present with weight loss, fatigue, loss of appetite and abdominal pain (intrahepatic cholangiocarcinomas) or jaundice (extra-hepatic cholangiocarcinomas). Subcapsular bile vessel rupture, due to intrahepatic cholangiocarcinoma, is an extremely rare clinical presentation, which is an emergent and potentially life-threatening complication. We report the case of a 79-year-old female patient suffering from an intrahepatic cholangiocarcinoma that completely obliterated the left main hepatic duct. This obstruction in intrahepatic bile flow had resulted in intraperitoneal rupture of subcapsular bile vessels (not infiltrated by the tumor) of the left liver lobe and formation of spontaneous biloma. The patient was admitted for acute abdominal pain. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) revealed the tumor and an upper abdominal fluid collection. Since the patient was hemodynamically stable and afebrile, a CT-guided percutaneous aspiration of the collection was undertaken, showing a biloma. A left hepatectomy was performed two weeks later and today, sixty months since the incident, the patient enjoys good health, with no signs of local recurrence or distant metastases. Intraperitoneal rupture of bile ducts and subsequent spontaneous biloma formation, due to an intrahepatic cholangiocarcinoma which completely obstructed the left main hepatic duct, is a unique situation and this is the first time to be reported. Prompt surgical management can lead to successful treatment of this rare and difficult entity.

Undifferentiated carcinoma of the head of pancreas with osteoclast-like giant cells presenting as a symptomatic cystic mass, following acute pancreatitis: Case report and review of the literature.

INTRODUCTION: Undifferentiated head of pancreas carcinoma with osteoclast-like giant cells (UC-OGC) is a rare neoplasm, with less than a hundred cases reported. We present such a case, in which the UC-OGC presented atypically as a cystic lesion following acute pancreatitis and led to late diagnosis. PRESENTATION OF CASE: A 75-year-old female patient, who had suffered acute pancreatitis three years ago, was referred with a diagnosis of osteoclast-like giant cell (OGC) tumor of the head of pancreas. She had suffered acute pancreatitis three years ago. Two years ago she developed abdominal pain, steatorrhea and weight loss. Abdominal computed tomography imaging showed a cystic mass in the head of the pancreas (maximum diameter 4cm). The initial diagnosis was pancreatic pseudocyst; however as the mass gradually increased in size and the patient continued to be symptomatic, a CT-guided biopsy was performed. Histological examination revealed an OGC pancreatic tumor. In laparotomy a large (9cm) encapsulated heterogeneous mass was found with partial involvement of the common hepatic artery. Pancreaticoduodenectomy was performed and the involved part of the common hepatic artery was replaced with a homologous graft from the major saphenous vein. Post-operative course was uneventful. Histology revealed an undifferentiated pancreatic adenocarcinoma with OGCs. She survived 10 months after the operation. DISCUSSION: Pancreatic undifferentiated carcinomas with OGCs are very rare neoplasms and can present with an atypical clinical picture. CONCLUSIONS: A symptomatic cystic lesion of the pancreas, which is growing in size, should be investigated promptly in order to exclude the presence of malignancy.

Surgical management of hydatid liver disease.

BACKGROUND: large retrospective clinical study describing the long-term experience of a single center in the surgical management of liver echinococcosis in an endemic area. METHODS: 232 patients were operated for liver hydatid disease between 1978 and 2012. Seventy-three patients (Group A) underwent a radical procedure (total pericystectomy or hepatectomy), while 145 (Group B) were treated with a more conservative method (partial cystectomy, with external drainage, omentoplasty or capitonnage) and 14 (Group C) received a combination of total and partial cystectomies. Morbidity, mortality, post-operative complications and recurrence rates in the long-term setting were retrospectively evaluated. RESULTS: Group A patients were treated with zero mortality and a morbidity rate of 10.95%. No recurrence was documented. In Group B, mortality reached 2.76%, (p = 0.153 compared to Group A) morbidity 24.13% (p = 0.021) and there were 10 cases of relapse (6.9%) at three-year complete follow-up (p = 0.989). Extrahepatic sites of disease were not uncommon. DISCUSSION: radical surgical procedures were better tolerated by patients and yielded better results in terms of recurrence rates.

Unusual locations of hydatid disease: a 33 year's experience analysis on 233 patients.

Hydatid disease is caused by the tapeworm Echinococcus granulosus and it is an endemic parasitic disease of the Mediterranean countries. Although the liver is the most involved organ by this disease, hydatidosis can be found anywhere in the human body. Rare forms of location may pose diagnostic and therapeutic dilemmas. Herein we report our experience with unusual located hydatid disease diagnosed and treated at our center the last 33 years. A total of 233 patients were treated for echinococcosis (91 males: 39% and 142 females: 61%) between 1980 and 2013 at our center. 18 of them (7, 8%) with uncommon located hydatid disease, were analyzed retrospectively. 18 patients (8 males and 10 females) were presented with unusual location of hydatid disease in our series. Two of them had only extrahepatic cysts (0, 9%). A total of 64 hydatid cysts with unusual location were analyzed. The most prevalent extrahepatic sites were peritoneal cavity and spleen. Total cystectomy with or without tube drainage or omentopexy was performed for hydatid cysts of the peritoneal cavity in our series. Splenectomy was performed in all cases of splenic hydatidosis. The mean time of post operative stay was 16, 3 days (range 7-35 days), morbidity 11% and mortality 5, 4%. Although echinococcosis is found most often in the liver and lungs, it seems that any organ can be involved by this zoonotic disease. The operating surgeon must always consider the possibility of unusual location of echinococcal cyst when dealing with patients with cystic mass in endemic areas, because any misinterpretation may result in unfavorable outcomes.

Non-secreting benign glucagonoma diagnosed incidentally in a patient with refractory thrombocytopenic thrombotic purpura: report of a case.

Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder, which may be idiopathic or secondary to a variety of diseases. However, there are very few reports of TTP in the context of pancreatic neoplasms. We report a case of relapsing TTP after initial treatment with plasmapheresis, corticosteroids, and rituximab, in a 59-year-old woman. During diagnostic work-up, a pancreatic lesion 35 × 25 mm in size was discovered incidentally and splenopancreatectomy was performed. The pathological diagnosis was benign glucagonoma. The hematological symptoms resolved completely after the procedure and 3 years later, the patient is well with no sign of recurrence of TTP or glucagonoma. To our knowledge, this represents the first documented case of a non-secreting benign pancreatic neuroendocrine tumor (glucagonoma) associated with TTP that is refractory to standard treatment.

Kinetics of circulating levels of miR-195, miR-155 and miR-21 in patients with breast cancer undergoing mastectomy.

BACKGROUND: MicroRNAs are small RNA molecules that negatively regulate the expression of the majority of proteins, mainly at the post-transcriptional level. Being stable in the circulation and resistant to storage handling, they are potentially promising biomarkers. MATERIALS AND METHODS: We measured RNA levels of three microRNAs with tumorigenic or angiogenic potential (miR-155, miR-195, and miR-21) in blood samples taken from patients with early breast cancer, both preoperatively and postoperatively. RESULTS: We found that persistently elevated postoperative levels of miR-195 were detected only in patients who developed early tumor relapse and that miR-155 levels tended to increase three days postoperatively (p=0.05) and fell below baseline one month post-surgery (p<0.05). We had no major findings for miR-21. CONCLUSION: The results of this pilot study indicate a possible involvement of miR-155 in surgery-induced angiogenesis and potential prognostic significance of high postoperative levels of circulating miR-195 in patients with breast cancer.

Impact of breast cancer surgery on angiogenesis circulating biomarkers: a prospective longitudinal study.

BACKGROUND: Debate about the potential effects that surgery might have on cancer cells dormancy and angiogenesis prompted us to investigate the impact of breast surgery on circulating angiogenesis modulating gene transcripts and proteins. METHODS: Blood samples from 10 female patients diagnosed with breast cancer and 6 with fibroadenoma were collected before surgery and post-operatively on days 3 and 7 (breast cancer patients only). A set of 84 angiogenesis-associated transcripts were assessed using quantitative PCR arrays, and circulating protein levels (vascular endothelial growth factor A (VEGFA), IL8 and fibroblast growth factor 2 (FGF2) were measured using ELISA in the same samples. The results were investigated against clinicopathological data and patient outcome. RESULTS: Plasma levels of VEGFA and IL8 after surgery were significantly elevated in the breast cancer group compared to the control group (P = 0.038 and P = 0.021, respectively). In the cohort of breast cancer patients, VEGFA increased on day 3 (P = 0.038) and declined on day 7 (P= 0.017), while IL8 did not change on day 3 but showed a significant decline on day 7 (P = 0.02). FGF2 levels did not change significantly over time. Regarding gene transcripts, we detected upregulation of a significant number of angiogenesis-specific genes in patients with breast cancer versus controls: sphingosine kinase 1(SPHK1), epidermal growth factor (EGF), vascular endothelial growth factor C (VEGFC), neuropilin 1 (NRP1), fibroblast growth factor (FGF1), laminin alpha 5 (LAMA5), collagen type IV alpha 3 (COL4A3), IL8, ephrin B2 (EFNB2), ephrin A3 (EFNA3), tyrosine endothelial kinase (TEK), integrin beta 3 (ITGB3), AKT1, thrombospondin 1 (THBS1), chemokine (C-C motif) ligand 11 (CCL11) and TIMP metallopeptidase inhibitor 3 (TIMP3). Surgery induced an altered expression in several keygenes in breast cancer patients. We identified an upregulation of COL4A3 and downregulation of chemokine (C-X-C motif) ligand 9 (CXCL9), EGF, FGF1, Kinase insert domain receptor (KDR), Placental growth factor (PGF), TIMP3 and VEGFC. CONCLUSION: Breast cancer patients have a different expression profile of circulating angiogenesis biomarkers compared to patients with fibroadenoma. Moreover, mastectomy promotes a transient increase of VEGFA and a shift in the expression patterns of a broad panel of angiogenesis-related circulating gene transcripts.

Gene mutations and molecularly targeted therapies in acute myeloid leukemia.

Acute myelogenous leukemia (AML) can progress quickly and without treatment can become fatal in a short period of time. However, over the last 30 years fine-tuning of therapeutics have increased the rates of remission and cure. Cytogenetics and mutational gene profiling, combined with the option of allogeneic hematopoietic stem cell transplantation offered in selected patients have further optimized AML treatment on a risk stratification basis in younger adults. However there is still an unmet medical need for effective therapies in AML since disease relapses in almost half of adult patients becoming refractory to salvage therapy. Improvements in the understanding of molecular biology of cancer and identification of recurrent mutations in AML provide opportunities to develop targeted therapies and improve the clinical outcome. In the spectrum of identified gene mutations, primarily targetable lesions are gain of function mutations of tyrosine kinases FLT3, JAK2 and cKIT for which specific, dual and multi-targeted small molecule inhibitors have been developed. A number of targeted compounds such as sorafenib, quizartinib, lestaurtinib, midostaurin, pacritinib, PLX3397 and CCT137690 are in clinical development. For loss-of-function gene mutations, which are mostly biomarkers of favorable prognosis, combined therapeutic approaches can maximize the therapeutic efficacy of conventional therapy. Apart from mutated gene products, proteins aberrantly overexpressed in AML appear to be clinically significant therapeutic targets. Such a molecule for which targeted inhibitors are currently in clinical development is PLK1. We review characteristic gene mutations, discuss their biological functions and clinical significance and present small molecule compounds in clinical development, which are expected to have a role in treating AML subtypes with characteristic molecular alterations.