Current Cancer Therapy Reviews - Volume 9, Issue 3, 2013

Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. The incidence of CRC is low up to the age of 45-50 years, but progressively increases with age, and men are at more risk than women. Studies done on Japanese immigrants in the USA, Asian Jewish immigrants to Israel and East European immigrants in Australia have revealed that they acquire the common CRC rates in the country of their adoption. There is no doubt whatsoever which environmental factors, probably diet [10], may account for these cancer rates. Excessive alcohol consumption and cholesterol-rich diet are associated with a high risk of colon cancer [11,12]. A diet poor in folic acid and vitamin B6 is also associated with a higher risk of developing colon cancer with an overexpression of p53 [13]. Eating pulses at least 3 times a week lowers the risk of developing colon cancer by 33%, after eating less meat, while eating brown rice at least once a week cuts the risk of CRC by 40%. These associations suggest a dose-response effect. Frequently eating cooked green vegetables, nuts and dried fruit, pulses and brown rice has been associated with a lower risk of colorectal polyps [14]. High calcium intake offers a protector effect against distal colon and rectal tumours as compared with the proximal colon. Higher intake of dairy products and calcium reduces the risk of colon cancer [15]. Taking an aspirin regularly after being diagnosed with colon cancer is associated with less risk of dying from this cancer, especially among people who have tumours with COX-2 overexpression [16]. Nonetheless, these data do not contradict the data obtained on a possible genetic predisposition, even in sporadic or non-hereditary CRC. Modifiable risk factors of CRC include smoking habit, physical inactivity, being overweight and obesity, eating processed meat and drinking alcohol excessively [17-19]. CRC screening programmes are possible only in economically developed countries. However, attention should be paid in the future to those geographical areas with ageing populations and a western lifestyle [20,21]. Sigmoidscopy screening done with people aged 55-64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%.

Nanotechnology has emerged as a "disruptive technology" that may provide researchers with new and innovative ways to diagnose, treat and monitor cancer. In fact, nanomedicine approaches have delivered several strategies, such as new imaging agents, real-time assessments of therapeutic and surgical efficacy, multifunctional, targeted devices capable of bypassing biological barriers to target and silence specific pathways in tumours. Of particular interest, has been the increased capability to deliver multiple therapeutic agents directly to bulk cancer cells and cancer stem cells that play a critical role in cancer growth and metastasis. These multifunctional targeted nanoconjugates are also capable of avoiding cancer resistance and monitor predictive molecular changes that open the path for preventive action against pre-cancerous cells, minimizing costs and incidence of relapses. A myriad of nanoconjugates with effective silencing and site-targeting moieties can be developed by incorporating a diverse selection of targeting, diagnostic, and therapeutic components. A discussion of the integrative effort of nanotechnology systems with recent developments of biomolecular interactions in cancer progression is clearly required. Here, we will update the state of the art related to the development and applications of nanoscale platforms and novel biomolecular players in cancer diagnosis, imaging and treatment.

Primary liver tumors and liver metastases are the two most common malignant liver tumors. In cases of unresectable malignant tumors, local ablative therapies are considered as the preferred option. These include transarterial chemoembolization, radioembolization, radiofrequency ablation, microwave ablation, percutaneous alcohol injection, cryotherapy and laser therapy. Local ablative therapies have the additive advantage of preserving the uninvolved liver parenchyma, and can be used in combination or as adjuvant to surgery or bridge to liver transplantation. MRI is more sensitive and accurate compared to CT in detecting and characterize malignant liver lesions pre- and post-therapy. The aim of this article is to describe the MRI appearance of post-treatment liver changes after a wide variety of local ablative therapies and discuss some of the new advances in post-treatment liver imaging.

KIT and FLT3 are class III trans membrane tyrosine kinases playing key roles in the control of hematopoietic stem cell survival and proliferation. KIT is mutated in about 2.5-3% of acute myeloid leukemia (AML) patients mainly by point mutations occurring at the level of tyrosine kinase domains. FLT3 is mutated in about 30% of AML patients, either by internal tandem duplication of the juxtamembrane domain or by point mutations occurring at the level of tyrosine kinase domains. All these types of mutations lead to the constitutive activation of KIT and FLT3 receptors, respectively. In some AML subsets, the occurrence of FLT3/ITD mutation is associated with a poor prognosis. These observations have represented the basis for the development of a large number of Tyrosine Kinase Inhibitors (TKIs) with activity against KIT and FLT3. Some of these inhibitors are still in the preclinical phase, but many have been tested in phase I/II/III clinical studies. Although these inhibitors when used as single agents have lead to a significant reduction of the number of leukemic blasts, they have produced only transient and limited clinical responses. This efficacy may be related to the limited inhibitory caefficacy of these inhibitors, occurrence of resistance and to the complexity of the genetic abnormalities occurring in AMLs. However, recently Quizartinib, a potent FLT3 inhibitor, showed an impressive rate of remission induction in patients with chemotherapy-refractory FLT3-ITD-positive AMLs, but most remissions do not meet classical criteria of complete remissions and instead represent clearance of bone marrow blasts with incomplete recovery of blood cell counts. However, the majority of these patients after an initial sustained response exhibit a leukemic relapse due to the rare pre-exisisting or new FLT3-ITD-TKD mutants surviving to the treatment with this drug and becaming driver leukemic clones. The combination of various types of FLT3 TKIs, including a type II TKI like Quizartinib with a type I FLT3 inhibitor efficiently targeting TKD mutants, such as Crenolanib, or the combination of FLT3 inhibitors with other molecularly targeted agents inhibiting other pathways activated in leukemic cells would determine a major progress in leukemia therapy. The efficacy of FLT3 TKIs in combination with standard anti-leukemic chemotherapeutics is also under evaluation in several combination clinical trials. It is expected that these trials could determine an improvement in the negative prognosis of AML patients with FLT3/ITD mutations.

Introduction: Until recently, there have been limited options for treatment of metastatic neuro endocrine tumors (NETs). Real life experience with newly developed targeted therapies for this condition is limited outside large referral centers. Case: Here we describe a 43 year old patient with metastatic NET of intestinal origin. The management of this patient illustrates a number of real life practical issues including effect of treatment interruption, secondary resistance to somatostatin analogues, availability and toxicity of new targeted agents, multiple lines of sequential treatment and local availability of specific investigations. This patient is enjoying a long progression free survival (29+ months) on a combination of Everolimus and Octreotide-LAR with a survival of 43+ months from diagnosis of metastatic disease. Conclusion: Patient with metastatic NETs can benefit from newly developed targeted therapies. However, they are best managed by multi-disciplinary teams in referral centers to guarantee adequate experience and specialist resources.