Ciência e terapia do câncer

Tumor budding, defined as the presence of single cancer cells or small clusters of fewer than five cells at the tumor invasive front, has been reported to be an independent prognostic factor for several cancers together with margin status, depth of invasion, lymph vascular invasion, and lymph node metastasis. Distant metastasis and poor prognosis were significantly more common in the higher budding group. In this short review, we focused on the studies related to tumor budding in several cancers including oral squamous cell carcinoma(OSCC) and showed the association among the intensity of tumor budding, risk of lymph node metastasis, and poor prognosis in OSCC is strongly supported by many studies. Moreover, arguments for the assessment of tumor budding, scoring system, stains to mark budding, specimens, and the association with epithelial mesenchymal transition (EMT) are also discussed.

MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNAs that negatively regulate gene expression by several mechanisms. Deregulation in expression of miRNAs has been reported in the pathogenesis of cancer. Accordingly, studies identified down regulation in the expression of miRNAs having tumor suppressor role and up-regulation in the expression of oncogenic miRNAs in different types of cancer. In response to these observations currently there are ongoing efforts to develop safe and effective miRNA-based therapeutics in the hope of fighting against cancer. This paper aimed at reviewing the role of miRNAs in tumorigenesis, and strategies for therapeutic targeting of miRNAs in cancer.

Background: Nivolumab and pembrolizumab are the first two US FDA-approved monoclonal antibodies targeting PD-1 for Hodgkin lymphoma (HL) and provide promising results in the relapsed/refractory setting (HL patients relapsing after autologous stem cell transplantation [ASCT], or with chemorefractory disease and/ or ineligible for ASCT). An interesting area of ongoing research is the possibility of combining different immune checkpoint inhibitors given concomitantly or sequentially in the attempt to maximize the patient responsiveness. Case report: A heavily pre-treated young woman affected by HL, after several attempts, obtained a complete response after ASCT thanks to the bridge with pembrolizumab. After relapse, the patient achieved again a complete response with nivolumab, bridging her to allotransplant. The patient is still in response to a year since the transplant. Discussion and Conclusion: This is the first report which witnesses the safety and the antitumor activity of interchangeable anti-PD1 monoclonal antibodies administered as a retreatment option and as a bridge to allotransplant in a patient who previously got an objective response to another anti-PD1 which brought her to autologous transplant. Retreatment with anti-PD1 monoclonal antibodies could be considered in therapeutic algorithm of relapsed/refractory HL.

Type I or invariant natural killer T cells belong to a unique lineage of innate T cells, which express markers of both T lymphocytes and NK cells, namely T cell receptor (TCR) and NK1.1 (CD161C), respectively. Thus, apart from direct killing of target cells like NK cells, and they also produce a myriad of cytokines which modulate the adaptive immune responses. Unlike traditional T cells which carry a conventional ab TCR, NKT cells express semiinvariant TCR – Va14-Ja18, coupled with Vb8, Vb7 and Vb2 in mice. In humans, the invariant TCR is composed of Va24-Ja18, coupled with Vb11.

Nivolumab, a humanized IgG4 programmed death-1 (PD-1) inhibitor antibody, is approved in Italy for advanced non small cell lung cancer (NSCLC), for advanced melanoma in association with ipilimumab, in second line renal cell carcinoma (RCC), in Hodgkin lymphoma relapsed after autologous stem cell transplantation and treatment with brentuximab vedotin, in head and neck squamous cell carcinoma progressed after platinum therapy and in locally advanced urothelial carcinoma unresectable or metastatic after failure of previous platinum therapy. Its immunogenic potential is well known, with described autoimmune-like syndromes, but no clear association is evident for hemolytic anemia. We report case of a 68-year-old man who developed hemolytic anemia after 28 cycles of treatment for advanced Squamous Cell Lung Cancer (SSC).

One hundred years ago, abnormal metabolism of cancer cell was regarded as one of the most important pathological features of malignancy. Recently, with the development of system biology, researchers regained the interest in regulating cancer metabolism. In 1920s’, Dr. Otto Warburg discovered that, even when oxygen is ample, malignant cells still prefer the anaerobic glycolysis, and the rate of glucose uptake is high while the overall glycolysis increases. Cancer cells divide faster than normal cells, hence they need more bioenergy, and they need to change their metabolism to produce the extra energy. In recent 20 years, the link between high rate of glycolysis and cancer was re-evaluated and has inspired enthusiasm upon research into the metabolism of cancer cells. Novel diagnostic methods and new drugs were created by the understanding of the features of cancer metabolism. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and prognosis. The purpose of this review is to focus on the mechanism of high rate of glycolysis in cancer and its significance in cancer diagnosis and therapies. The regulatory network of cancer is complex, system biology might help us to find the clue. There are evidences showing that mixture of drugs has therapeutic advantages in clinical practice. Combinations of anti-neoplasm drugs have already been administered with encouraging results. Therefore, the multi-targeted MCA advised therapy might be the most promising strategy for cancer. The study for novel inhibitors from medicinal herbs are now ongoing. We believe, there will be more and more therapeutic strategies coming in the near future to help human beings fighting with cancer.