ABSTRACT
Heregulins (HRGs) bind to the receptors HER3 or HER4, induce receptor dimerization, and trigger downstream signaling that leads to tumor progression and resistance to targeted therapies. Increased expression of HRGs has been associated with worse clinical prognosis; therefore, attempts to block HRG-dependent tumor growth have been pursued. This manuscript summarizes the function and signaling of HRGs and review the preclinical evidence of its involvement in carcinogenesis, prognosis, and treatment resistance in several malignancies such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and breast cancer. Agents in preclinical development and clinical trials of novel therapeutics targeting HRG-dependent signaling are also discussed, including anti-HER3 and -HER4 antibodies, anti-metalloproteinase agents, and HRG fusion proteins. Although several trials have indicated an acceptable safety profile, translating preclinical findings into clinical practice remains a challenge in this field, possibly due to the complexity of downstream signaling and patterns of HRG, HER3 and HER4 expression in different cancer subtypes. Improving patient selection through biomarkers and understanding the resistance mechanisms may translate into significant clinical benefits in the near future.
ABSTRACT
The National Hospice and Palliative Care Organization estimates that in 2006, 44.1% of hospice admissions had cancer as primary diagnosis, still representing the most common diagnosis in this level of care. In the recent years, the treatment of cancer sustained unprecedented advances with better understanding of cancer biology. Growth factor receptors emerged as target for effective therapy providing significant clinical benefit, for example epidermal growth factor receptor 2 or human epidermal growth factor receptor 2 + breast cancer disease has been routinely treated with trastuzumab, a monoclonal antibody, with significant survival benefit. Other cancers had their treatment changed by targeted therapy. This article reviews concepts of cancer cell biology and analyze the current standard of care use of targeted therapy. The data highlights aspects of targeted therapy important to health care professionals involved in hospice and palliative care of patients with cancer.
