Mitochondria have emerged as important pharmacological targets due to their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge on mitochondria. Cancer cells can also acquire a hybrid phenotype in which both glycolysis and OXPHOS can be utilized. This hybrid phenotype can facilitate metabolic plasticity of cancer cells more specifically in metastasis and therapy-resistance. In light of the metabolic heterogeneity and plasticity of cancer cells that had until recently remained unappreciated, strategies targeting cancer metabolic dependency appear promising to develop novel and effective cancer therapeutics.
Mitochondria and CancerAbnormal mitochondrial morphology, functions, and dynamics have long been associated with malignant transformation. Otto Warburg in the 1920s was one of the first to observe this phenomenon where cancer cells utilize glycolysis, even under oxygen rich conditions, and produce excess lactate, a process defined as "aerobic glycolysis", which is often referred to as the "Warburg effect" [1,2]. This finding suggested that mitochondrial dysfunction is the hallmark of cancer tumorigenesis and became the foundation for the visual detection of cancer via the development of positron emission tomography (PET) imaging, both as a staging tool and to evaluate response to therapy. Another observation that supported this viewpoint was the production of high levels of mitochondrial ROS. Enhanced ROS leads to the activation of cellular signaling cascades and oncogene activation that result in cell proliferation and genomic instability [3,4]. However, this view was challenged when it was demonstrated that mitochondria are not wholly dysfunctional in cancer and in fact, produce similar levels of intermediates of the tricarboxylic acid (TCA) cycle and fatty acid oxidation as non-cancerous cells [5][6][7]. Even while aerobic glycolysis is increased in an oxygen-rich
The baseline skills assessment suggests a need for physician training in cancer risk communication and shared decision making for patients with low HL. We are determining the effectiveness of teaching methods, required resources and long-term feasibility for a CME program.
Purpose
Ipilimumab was the first FDA-approved agent for advanced melanoma to improve survival and represents a paradigm shift in melanoma and cancer treatment. Its unique toxicity profile and kinetics of treatment response raise novel patient education challenges. We assessed patient perceptions of ipilimumab therapy across the treatment trajectory.
Methods
Four patient cohorts were assessed at different time points relative to treatment initiation: (1) prior to initiation of ipilimumab (n = 10), (2) at weeks 10–12 before restaging studies (n = 11), (3) at week 12 following restaging studies indicating progression of disease (n = 10), and (4) at week 12 following restaging studies indicating either a radiographic response or disease stability (n = 10). Patients participated in a semistructured qualitative interview to assess their experiences with ipilimumab. Quality of life was assessed via the Functional Assessment of Cancer Therapy-General and its Melanoma-specific module.
Results
Perceived quality of life was comparable across cohorts, and a majority of the sample understood side effects from ipilimumab and the potential for a delayed treatment response. Patients without progression of disease following restaging studies at week 12 held more positive views regarding ipilimumab compared to patients who had progressed.
Conclusion
Patients generally regarded ipilimumab positively despite the risk of unique toxicities and potential for delayed therapeutic responses; however, those with progression expressed uncertainty regarding whether taking ipilimumab was worthwhile. Physician communication practices and patient education regarding realistic expectations for therapeutic benefit as well as unique toxicities associated with ipilimumab should be developed so that patients can better understand the possible outcomes from treatment.
Regional nodal metastases were observed among patients who presented with tumours >T2b. Tumour size and the AJCC TNM designations correlate with metastasis and should be reported more often for eyelid SCCs to allow comparisons across centres.
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