Colorectal cancer is one of the most common cancer types and still a major public health problem. Approximately a half of the patients develop metastasis during the course of disease. Prognosis of metastatic colorectal cancer (mCRC) is poor with best supportive care alone (median survival: 6 months). Fortunately, combination chemotherapy has significantly improved survival up to 17–22 months. Cetuximab and panitumumab, the two monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR), provide significant clinical benefit in only RAS wild (WT) mCRC. Major side effects are skin toxicity, infusion reactions, fatigue, and electrolyte imbalances. When these mAbs are combined with chemotherapy, overall survival could be as long as 24 months. However, RAS WT status does not ensure response to anti-EGFR mAbs. In addition, RAS WT patients consequently develop resistance to these agents after an initial responsive period. Therefore, understanding the primary and secondary resistance mechanisms apart from RAS status is very important to improve outcomes of mCRC patients. Oncogenic activation of EGFR downstream signaling effectors (KRAS, BRAF, PTEN, and PIK3CA) appears to be the main components of resistance. In future, a comprehensive biomarker analysis will probably help to identify the mCRC patients who will truly benefit from anti-EGFR mAbs.
Part of the book: Colorectal Cancer
Throughout the last three decades, there has been a notable shift in the epidemiology of head and neck cancer (HNC) worldwide. A rapidly spreading subtype of HNCs is caused by human papillomavirus (HPV) infection. HPV-related cancers are now considered to constitute 30–65% of all HNC cases and 50–80% of oropharyngeal cancers. HPV-positive oropharyngeal cancers have a unique demographic profile and tumor biology characteristics. HPV-associated patients predominantly consist of younger men with better performance status and fewer comorbid diseases. They have better dentition, higher numbers of oral sex partners, and use less amount of tobacco or alcohol, higher amount of marijuana compared with HPV-negative patients. In addition, patients with HPV-positive tumors have a 60–80% reduced mortality rates, a finding that was confirmed by multiple trials and led to several ongoing deintensification studies. This chapter describes epidemiologic features of HPV-positive HNC, risk factors for HPV infection and HPV-associated oropharyngeal cancer, HPV detection methods, mechanisms of carcinogenesis and improved treatment response, and the impact of HPV status on clinical outcome as well as deintensification approaches and potential of vaccination.
Part of the book: Human Papillomavirus