[#2018-09] Maitake Zhang, Michael et al. Enhanced Anticancer Effect by Combination of Proteoglucan and Vitamin K3

Bladder cancer is the second common genitourinary malignancy next to prostate cancer in the United States.1 Nearly 82,000 new cases would be diagnosed and ~ 17,000 people may die this year (2018).1 Approximately 75% of all newly diagnosed cases will present nonmuscle invasive bladder cancer (NMIBC) including stage Ta, T1 and carcinoma in situ,2,3 while other 25% are muscle invasive bladder cancers (MIBCs) or metastatic cancers.3 The primary treatment for NMIBC is transurethral resection of bladder tumor (TURBT);4 however, NMIBC following TURBT has a high recurrence rate of up to 70%, of which ~ 20% may progress to advanced MIBC.5 The reason(s) for this high recurrence is/are not fully understood, but a multifocal origin of disease, as well as intrinsic acquired resistance to drugs, appears to be a major cause of such a high incidence of disease relapse.6 Hence, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, MIBC. To reduce or minimize the risk of tumor recurrence, intravesical immunotherapy with bacillus Calmette–Guerin (BCG), an attenuated strain of Mycobacterium bovis, is often recommended following TURBT.5,7 This intravesical BCG administration is indeed the most effective therapy among currently available therapeutic options – it has been shown to alter disease progression, reduce recurrence, and increase survival.7,8 However, up to 80% of patients will have recurrence and up to 45% of them may progress to MIBC within 5 years.9 In addition, its benefits are also outweighed by its severe side effects including cystitis, fever, sepsis, and allergic reactions10 so that BCG treatment is often withdrawn from the recommended 1–3 year treatment protocol. These concerns thus limit its use in clinical practice and demonstrate the need for a nontoxic, safe, effective treatment modality with few side effects.