Volume 11 Issue 5, May 2014

The use of antiangiogenic drugs, such as bevacizumab, represents an appealing intervention against cancer. However, not all malignancies are equally responsive to such treatment. Recent trials demonstrate the efficacy of this drug for advanced-stage cervical cancer and, despite limitations, bevacizumab provides an important clinical respite for most patients with progressive glioblastoma.

A large definitive trial comparing the use of sentinel lymph node biopsy and elective lymph node dissection to observation in patients with intermediate thickness melanomas fails to show improved melanoma-specific survival. These results demand reconsideration of the routine use of sentinel lymph node biopsy in the treatment of primary melanoma.

The MSLT-1 study compared sentinel lymph node biopsy (SLNB) with nodal observation in patients with localized cutaneous melanoma. The final results of the trial—conducted from 1994 to 2002—strongly support using SLNB in staging patients with melanomas ≥1.0 mm in thickness, but the optimal staging approach for thinner melanomas is unanswered.

The final analysis of the MSLT-1 trial confirms that sentinel lymph node biopsy (SNLB) does not improve survival in patients with melanoma >1 mm thickness. Subgroup analyses remain inconclusive. SNLB provides prognostic information for adjuvant therapy decisions, as recent data indicate that adjuvant therapies are effective in patients with positive sentinel nodes with an ulcerated primary.

In September 2012, over 100 experts in cancer research in Africa met in London to discuss the challenges in carrying out high-quality research in this continent. This Review summarizes the discussions and recommendations of this meeting and many examples of successful programmes that have enhanced the development of research in Africa. It also discusses the next steps required to create programmes that will enable evidenced-based cancer control approaches.

Individuals with Li-Fraumeni syndrome, who carry germline mutations in theTP53 gene that encodes the tumour-suppressor protein p53, are at high risk of developing cancers in multiple organs. In this Review, considerations for cancer screening and management in carriers of TP53mutations are discussed, and an evidence-based approach to cancer surveillance in such individuals is proposed.

Identification of the optimal dose remains a key challenge in drug development. The standard approach that is based on identifying the maximum tolerated dose does not take into account important aspects of clinical pharmacology for newer targeted agents. The authors discuss adaptations to dose-finding trials for molecularly-targeted agents that enable more-efficient trials in the future in terms of costs and, most importantly, optimal patient benefit.

Chemotherapeutic agents targeting thymidylate biosynthesis, and particularly the enzyme thymidylate synthase, have now been key cancer therapies for 60 years. In this article, the classic and novel approaches to targeting this metabolic pathway and strategies for overcoming drug resistance mechanisms are comprehensively reviewed.