Biologically-Based Complementary and Alternative Medicine (CAM) Use in Cancer Patients: The Good, the Bad, the Misunderstood

Approximately 30% of human lung cancers acquire mutations in either Keap1 or Nfe2l2 , resulting in the stabilization of Nrf2, the Nfe2l2 gene product, which controls oxidative homeostasis. Here, we show that heme triggers the degradation of Bach1, a pro-metastatic transcription factor, by promoting its interaction with the ubiquitin ligase Fbxo22. Nrf2 accumulation in lung cancers causes the stabilization of Bach1 by inducing Ho1, the enzyme catabolizing heme. In mouse models of lung cancers, loss of Keap1 or Fbxo22 induces metastasis in a Bach1-dependent manner. Pharmacological inhibition of Ho1 suppresses metastasis in a Fbxo22-dependent manner. Human metastatic lung cancer display high levels of Ho1 and Bach1. Bach1 transcriptional signature is associated with poor survival and metastasis in lung cancer patients. We propose that Nrf2 activates a metastatic program by inhibiting the heme- and Fbxo22-mediated degradation of Bach1, and that Ho1 inhibitors represent an effective therapeutic strategy to prevent lung cancer metastasis.

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles. We identified reporting bias in 40 indications comprising around 50 different pharmacological, surgical (e.g. vacuum-assisted closure therapy), diagnostic (e.g. ultrasound), and preventive (e.g. cancer vaccines) interventions. Regarding pharmacological interventions, cases of reporting bias were, for example, identified in the treatment of the following conditions: depression, bipolar disorder, schizophrenia, anxiety disorder, attention-deficit hyperactivity disorder, Alzheimer's disease, pain, migraine, cardiovascular disease, gastric ulcers, irritable bowel syndrome, urinary incontinence, atopic dermatitis, diabetes mellitus type 2, hypercholesterolaemia, thyroid disorders, menopausal symptoms, various types of cancer (e.g. ovarian cancer and melanoma), various types of infections (e.g. HIV, influenza and Hepatitis B), and acute trauma. Many cases involved the withholding of study data by manufacturers and regulatory agencies or the active attempt by manufacturers to suppress publication. The ascertained effects of reporting bias included the overestimation of efficacy and the underestimation of safety risks of interventions. In conclusion, reporting bias is a widespread phenomenon in the medical literature. Mandatory prospective registration of trials and public access to study data via results databases need to be introduced on a worldwide scale. This will allow for an independent review of research data, help fulfil ethical obligations towards patients, and ensure a basis for fully-informed decision making in the health care system.