Malignant pleural mesothelioma (MPM) is a fatal malignancy associated with asbestos exposure. Although various therapies have been used in the past, including surgery, chemotherapy, radiotherapy, immunotherapy, and more recently targeted therapy, prognosis still remains poor. Radical surgery including extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) is being offered to obtain maximal cytoreduction in the context of multimodality therapy in patients with MPM. Growing evidence suggests that EPP might be detrimental, while recent reports suggest that P/D is better tolerated, producing low mortality and morbidity and allowing patients to receive adjuvant therapies in the form of either chemotherapy alone, or combined chemoradiotherapy. Many now believe that P/D should be the default procedure in multimodality regimens, although this remains to be proven in a large randomized trial. Apart from its therapeutic role, surgery has also an important role to play in pleural mesothelioma in establishing or refining diagnosis and in controlling symptoms and improving quality of life in many patients whose life expectancy is limited. Recent progress in molecular analyses and biomarkers should help with patient selection for surgery, immunotherapy and systemic therapies in the near future.
The search for molecular biomarkers that predict the likely response to targeted treatments for metastatic colorectal cancer (mCRC) has yielded many promising candidates, yet only the (K)RAS mutation has so far been incorporated into clinical practice. Other promising biomarkers of response to anti-angiogenic agents and the multikinase inhibitor, regorafenib, are currently under investigation in ongoing studies. While a growing understanding of cancer signaling pathways in mCRC presents multiple opportunities for the development of tumor-targeted therapies, inter- and intra-tumor heterogeneity and the dynamic process of tumor evolution during treatment present major challenges to biomarker research and drug development. Overcoming these challenges requires the application of novel approaches to the assessment of biomarkers and innovative clinical trials that employ statistical approaches that maximize efficiency and minimize exposure to underperforming treatments. Ongoing, contemporary biomarker-driven studies in mCRC have already yielded salient lessons that will inform the design of future studies. These will also benefit from the combined expertise of major research consortia using systems biology approaches to the identification and validation of predictive biomarkers in mCRC. With such a powerful global commitment to biomarker research in mCRC, there seems little doubt that before too long, new predictive biomarkers will be available to help guide clinical decision-making in mCRC, ensuring the right treatment is selected for the right patient at the right time.
There have been tremendous advances in our understanding of the molecular etiology of uveal melanomas (UMs) in recent years that have allowed clinicians to accurately stratify patients on the basis of their risk of developing metastasis. Risk stratification in UM is now a very advanced field and is incorporated into routine care for the majority of patients, for example, with screening strategies. Such stratification also affords patients and clinicians the opportunity to evaluate the potential benefits of entering into clinical trials. However, the ultimate utility of our improved knowledge must be the development of targeted therapies, which bring about tangible improvements in patient survival. To date this aim is yet to be realized. From the Department of Molecular and Clinical Cancer Medicine, Liverpool Ocular Oncology Research Group, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom (S.L.L., H.K., S.E.C.); and Ocular Oncology Service, University of California, San Francisco, California (B.E.D.). Correspondence: Sarah L. Lake, B.Sc., Ph.D., Department of Molecular and Clinical Cancer Medicine, Liverpool Ocular Oncology Research Group, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom (s.l.lake@liv.ac.uk).
