Update on cancer therapeutics最新文献

The immunomodulatory drug class has a broad range of biological effects with applications both within and outside oncology, and the oral bioavailability of these compounds makes them attractive agents. Thalidomide, the parent compound, was introduced into oncology over a decade ago to test many of its interesting pre-clinical features. While activity was notable in multiple myeloma, there were signals of activity in other malignancies. Multiple combinations have been developed and tested both in relapsed and front-line treatment of multiple myeloma. Based on modifications of the original drug, two derivatives, lenalidomide and pomalidomide, were developed and have been tested clinically. Lenalidomide is more potent in vitro than thalidomide and has demonstrated significant activity in multiple myeloma as well as myelodysplastic syndromes. Clinical activity has been noted in other malignancies too suggesting a broader range of activity. Multiple combinations have been tested as well in the relapsed and upfront setting. Pomalidomide demonstrated increase potency as well in vitro and has just begun early phase clinical testing.

Angiogenesis plays a crucial role in the survival, proliferation, and metastatic potential of several tumors, including genitourinary (GU) cancers. Over the last decade, increasing basic science and clinical research have led to the approval of several angiogenesis inhibitors. GU tumors are unique in its pathogenesis whereby specific pathways, such as involvement of the Von Hippel-Lindau gene in clear cell renal cell cancer and aberrant overexpression of vascular endothelial growth factor in prostatic cancers and transitional cell bladder cancers, allow for potential targeting using angiogenesis inhibitors. This review discusses the biologic pathways as well as the rationale for using angiogenesis inhibitors in renal cell, prostate, and transitional cell bladder cancers. This review also focuses on pivotal trials and emerging data on the use of these inhibitors.

Traditional treatment options for bladder cancer include transurethral resection and intravesical Bacillus Calmette Guerin for early stage disease and cystectomy or radiation therapy (with or without chemotherapy) for muscle-invasive disease. Platinum-based chemotherapy improves patient outcomes in both the perioperative and metastatic setting. Despite an increase in new therapeutic options over the past decade for many cancer patients, similar advances in bladder cancer are limited. In recent years, an improved understanding of the molecular forces driving bladder cancer development and progression has unfolded. These discoveries create a set of innovative therapeutic opportunities in bladder cancer. This review examines novel anti-cancer agents currently in clinical trials with preclinical rationale to support evaluation in bladder cancer. In addition, strategies to match a patient's tumor to the most appropriate agent are discussed. This may provide a more rational approach to evaluating the role of emerging anti-cancer agents in bladder cancer.

Breast cancer treatment has evolved dramatically in the last few years. Despite the benefit of anthracyclines, taxanes and trastuzumab for patients with metastatic and early breast cancer, the challenges of de novo and acquired resistance are still present. With advances in the molecular characterization of breast cancer, patient selection and individualization of treatment has taken on singular importance. Three main types of breast cancer have been reported to date: (a) HER-2 positive; (b) basal-like; and (c) luminal breast cancer. A large number of new agents now target different receptors and signalling pathways that sustain cancer survival and proliferation. In this review we highlight the novel molecules currently being tested in clinical trials that have or will have the potential to change our daily clinical practice; in particular, we focus on molecules used in the treatment of HER-2 positive and basal-like breast cancer patients.