RESUMO
MALT lymphoma is a non-Hodgkin lymphoma developing from B cells and is a type of marginal zone lymphoma. It can develop in any organs, but no case of primary cardiac location has yet been reported. We report the first observation of a primary epicardial MALT lymphoma mimicking a compressive pericardial syndrome. (Level of Difficulty: Advanced.).
RESUMO
The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases (CDKs) is a hallmark of cancer. The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs. In particular, third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition, exhibiting a perfect balance between anticancer efficacy and general toxicity. To date, three selective CDK4/6 inhibitors have received approval from the U.S. Food and Drug Administration (FDA), and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers. In this perspective, we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells, analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment, review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds, explain the mechanisms associated with CDK4/6 inhibitor resistance and describe solutions to overcome this issue, and briefly introduce proteolysis targeting chimera (PROTAC), a new and revolutionary technique used to degrade CDK4/6.
RESUMO
Mutations and epigenetic alterations are key events in transforming normal cells to cancer cells. Mantle cell lymphoma (MCL), a non-Hodgkin's lymphoma of the B-cell, is an aggressive malignancy with poor prognosis especially for those patients who are resistant to the frontline drugs. There is a great need to describe the molecular basis and mechanism of drug resistance in MCL to develop new strategies for treatment. We reviewed frequent somatic mutations and mutations involving the B-cell pathways in MCL and discussed clinical trials that attempted to disrupt these gene pathways and/or epigenetic events. Recurrent gene mutations were discussed in the light of prognostic and therapeutic opportunity and also the challenges of targeting these lesions. Mutations in the ATM, CCND1, TP53, MLL2, TRAF2 and NOTCH1 were most frequently encountered in mantle cell lymphoma. Translational models should be built that would assess mutations longitudinally to identify important compensatory, pro-survival and anti-apoptic pathways and actionable genetic targets.
Assuntos
Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , Mutação , Linfócitos B/metabolismo , Linhagem Celular Transformada , Aberrações Cromossômicas , Ciclina D1/genética , Metilação de DNA , Proteínas de Ligação a DNA/genética , Epigênese Genética , Humanos , Proteínas de Neoplasias/genética , Medicina de Precisão , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Receptor Notch1/genética , Recidiva , Indução de Remissão , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/genética , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
Multiple Myeloma and Mantle Cell Lymphoma are well defined hematological malignancies. Understanding of their pathogeneses has led to new therapies and increased survival. We report on a 64-yr-old female who was diagnosed with mantle cell lymphoma in 2003, then multiple myeloma in 2010. We identified only few other cases of concomitant MM and MCL. We also explored the importance of t(11;14)(q13;q32). The development of these two disorders in the same patient may simply be due to chance; however, it may also represent a common genetic hit affecting the B-cell population leading to development of two different malignancies.