Current Cancer Therapy Reviews - Volume 8, Issue 1, 2012

Current Cancer Therapy Reviews is now in its 8th year and relatively well known (not least for the brilliant collage at the front cover). According to the Cancer Statistics, 2011, published in the American Cancer Society's journal: “CA: A Cancer Journal for Clinicians”, a total of 1,596,670 new cancer cases and 571,950 deaths from cancer are projected to occurr in the U.S. in 2011. These numbers rise some skepticism regarding whether clinicians and scientists are winning the “War on Cancer”, a health metapher, introduced by U.S. President R. Nixon in his State of the Union speech, and he signed later on December 23 the National Cancer Act of 1971. Yes, we have made progress over the last 40 years in the war against cancer. Maybe not as much as we all hoped. The major killer cancers such as colon, breast and prostate steadily decline, which might have to do with better methods of early detection and treatment. The search for the ultimate weapon, the magic bullet that will “cure” cancer, is unlikely to be a single “cure for cancer”. There are more than 200 recognized types of cancer and their causes are myriad. Within a medial oriented scientific society and in a period of a high tide for clinical cancer research, it becomes increasingly important to communicate in a timely manner the advances in translational cancer research, alongside with clinical findings. Current Cancer Therapy Reviews will become a venue and forum for scientists and clinicians alike - above all from those countries just opening the doors to excellent clinical cancer research - to advocate their development of novel strategies, including academia, biotechnology/pharmaceuticals, their National Cancer Institutes and funding agencies. In order to meet our objects, the review process is paramount to provide fair reviews - and we are committed to rapid, rigorous, and constructive reviews, even to attract best articles from clinicians who are working under more laborious conditions to put together their clinical results as clinicians in the Western world might to experience. A particular emphesis of Current Cancer Therapy Reviews will be to create relationship with the worldwide community of clinicians in order to reflect the rapid international sharing of clinical informations and ultimately to promote -- also in and for different cultures and societies - the advances published as reviews or originale articles in Current Cancer Therapy Reviews. As Editor - in Chief, I am very grateful to all, who contribute to the success of this journal by writing reviews, originale articles and to serve as peers. I invite the readers, the authors and the reviewers of the journal to join the Editors and Editorial Advisory Board Member to pursue through the individual publishing policy of this journal our ultimate goal of conquering cancer.

The 2008 WHO classification system for hematological malignancies is comprehensive and requires the integration of histopathologic/cytomorphological, immunophenotypic, cytogenetic, and molecular data. Myeloid neoplasms include acute myeloid leukemia, myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), MDS/MPNs, and myeloid and/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements. The myeloproliferative neoplasms are now divided into chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PM), systemic mastocytosis (SM), chronic eosinophilic leukemia (CEL), not otherwise specified (NOS), chronic neutrophilic leukemia (CNL), and unclassifiable MPN. Some of the essential changes from the previous 2001 version include the following: 1. Separation of the myeloid and/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements from the MPN category and distinction from CEL 2. Separation of CEL, NOS from Hypereosinophilic syndrome 3. Inclusion of SM in the MPN category These changes have primarily resulted from new genetic findings. The diagnosis of CML still requires the presence of BCRABL1; however, additional MPN-associated molecular markers have been identified in the non-CML MPNs and entities to be separated from CEL, NOS. Additional MPN-associated markers include mutations of JAK2, MPL, TET2, and KIT. JAK2 V617F is found in most patients with PV, ET, or PV and may be used as a clonal marker. The diagnostic utility of MPL and TET2 mutations is limited by low mutational frequency. In SM, the presence of KIT D816V is expected but not essential for diagnosis. CEL, NOS should be distinguished from both PDGFR-rearranged or FGFR1-rearranged neoplasms and Hypereosinophilic syndrome. In addition, entities within the MDS/MDS category may be difficult to distinguish from MPNs. This Hot Topic issue reviews the histopathologic/cytomorphological with the pertinent immunophenotypic, cytogenetic, and molecular features in the various MPNs and MDS/MPNs and illustrate their integration into practical diagnostic algorithms and indications of disease progression. In pertinent entities, possible targeted therapies are also included.

Chronic myelogenous leukemia, BCR-ABL1+ (CML) is a myeloproliferative neoplasm characterized by a BCRABL fusion gene and almost always exhibits the characteristic cytogenetic finding t(9;22)(q34;q11). The protein product of BCR-ABL1 is a constitutively active tyrosine kinase whose function is intrinsic to CML pathogenesis. Patients present with leukocytosis and often splenomegaly and prominent marrow hypercellularity with marked myeloid hyperplasia and basophilia in most cases. Unlike acute leukemias, the neoplastic myeloid cells in CML exhibit a full spectrum of maturation at the early stages of disease, but if untreated CML inexorably progresses to an acute leukemia. The recent development BCR-ABL1 tyrosine-kinase inhibitors has profoundly changed the clinical course of patients with CML; most patients achieve long-term remissions if they are treated in the early part of the disease course. Monitoring of resistance to tyrosine-kinase inhibitors and assessment for disease progression are critical in current CML management. Therapeutic approaches, including targeted therapy, is discussed.

Myeloproliferative neoplasms (MPNs) are clonal bone marrow (BM) proliferations that most often manifest as increased peripheral blood (PB) counts and/or splenomegaly. Unlike myelodysplastic syndromes, the hemopoiesis in MPN is effective, leading to the increased peripheral counts; unlike the acute leukemias, there is intact maturation of all hematopoietic lineages. The main MPN entities discussed in this chapter are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The uncommon MPN entities of chronic neutrophilic leukemia and unclassifiable MPN are also discussed. An activating point mutation in the JAK2 gene underlies the pathogenesis of many MPN, including almost all cases of polycythemia vera and about half of essential thrombocythemia and primary myelofibrosis cases. Accurate diagnosis of MPN involves distinguishing these neoplasms from reactive causes of increased PB counts as well as appropriate classification of MPN into specific entities. The diagnosis of MPN requires an integration of clinical features, BM morphology, and genetic tests, in particular JAK2 mutation analysis. Therapeutic approaches, including targeted therapy as pertinent, are also discussed for each entity.

Chronic eosinophilic leukemia, NOS (CEL, NOS) is considered a myeloproliferative neoplasm and is defined as a clonal proliferation of eosinophil precursors. This review presents the definition and characteristic cytomorphological, immunophenotypic, cytogenetic, and molecular features of CEL, NOS and discusses in depth the differential diagnoses. Following this presentation, the review then focuses on therapeutic approaches, including targeted therapy.

Mastocytosis or mast cell disease represents a clonal, neoplastic proliferation of mast cells that can present in one or multiple organs, varying from indolent to aggressive disorders in adult and pediatric patients. This review presents the definition of the various forms of mastocytosis along with the characteristic cytomorphological, immunophenotypic, cytogenetic, and molecular features and discusses in depth the differential diagnoses. Following this presentation, the review then focuses on therapeutic approaches, including targeted therapy.

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 result from formation of a fusion gene encoding an aberrant tyrosine kinase. The cell of origin in those neoplasms associated with abnormalities of PDGFRA or FGFR1 is a mutated pluripotent (i.e., myeloid-lymphoid) stem cell, and thus the development of myeloid and lymphoid neoplasms associated with these abnormalities. Reported neoplasms associated with abnormalities of PDGFRB have been only myeloid in origin. This review presents the definitions and characteristic cytomorphological, immunophenotypic, cytogenetic, and molecular features of these neoplasms and discusses in depth the differential diagnoses. Following this presentation, the review then focuses on therapeutic approaches, including targeted therapy.

The myelodysplastic/myeloproliferative neoplasms represent disorders, which at initial presentation, demonstrate overlapping features of myelodysplasia and myeloproliferation. Entities included in this group of neoplasms are chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic/ myeloproliferative neoplasm, unclassifiable (including refractory anemia with ring sideroblasts associated with marked thrombocytosis). This review discusses each of these entities separately, including their characteristic cytomorphological, immunophenotypic, cytogenetic, and molecular features, differential diagnoses, and therapeutic approaches (including targeted therapy).

Recent discoveries in epidemiology and molecular epidemiology suggest a link between cancer risk, cancer progression and diabetes risk factors and treatment. Obesity, physical inactivity, smoking, mal nutrition and age are common risk nominators for both diseases. Furthermore due to these risk factors, tumor patients are often comorbid with diabetes type 2. Therefore, it is an urgent need in order to meet at least one risk factor - obesity and mal nutrition - to show that - in a scientifically well-based manner - ethnopharmacology can provide views on plants with health informations. Apart from epidemiological evidence, selected botanicals have to be proven in preclinical and cellular settings, in animal studies for the proof of principle and in clinical trials for their potentials as dietary nutritional care. We have shown here for the first time according to this scientific sequencing of evaluation that a special water soluble Bitter Melon powder is a first candidate to be included into personalized diabetes type 2 and antitumor protocols as dietary supportive care to control the carbohydrate metabolism. The proof of principle to decrease blood glucose values in db/db mice by a Bitter Melon powder was demonstrated and a prospective, randomized, double-blinded and Placebo-controlled trial in diabetes type 2 patients, although continuously throughout the trial under conventional oral therapy, gave evidence for a Bitter Melon powder to be able to decrease HbA1c in a four-months intervention. This study highlights the importance of a significantly evaluated botanical as supportive diet care in tumor and diabetes type 2 patients.