Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect

Immunotherapy and non-muscle-invasive bladder cancer: an idea from the 19th century

“…ICI that target both PD-1 and PD-L1 could reactivate cytotoxic T cells to fight tumor cells (17). Another investigated mechanism of resistance to BCG is, that BCG can prevent the expression of TNF-α-mediated p53 consequently attenuating cell TNF-α-mediated apoptosis (18). Therefore, by combining BCG therapy to PD-L1 inhibitors (either intravesical or systemic) or to TNF-α, we might be able to overcome these resistance mechanisms, inducing a more prolonged response to BCG instillation, preventing relapse, overcoming resistances, and making refractory patients sensible to BCG.…”

Vertebral Osteomyelitis Secondary to Bacillus Calmette-Guérin Instillation Therapy for Transitional Cell Carcinoma In Situ

“…Cytokeratin stain is negative for carcinoma AFB: acid-fast bacilli; PAS: periodic acid-Schiff; GMS: Grocott methenamine-silver Discussion M. bovis is primarily a zoonotic pathogen found in cattle and other livestock and domesticated animals [12]. The potential for the use of microbial products for the treatment of cancer was first noted in the late 1800s and the utilization of intravesical BCG was initiated with its first successful use for treatment in 1976 [3]. Intravesical BCG therapy is now the standard of care for bladder cancer, especially in the post-TURBT setting [2][3][4][5][6][7][8][9][10].…”

“…The potential for the use of microbial products for the treatment of cancer was first noted in the late 1800s and the utilization of intravesical BCG was initiated with its first successful use for treatment in 1976 [3]. Intravesical BCG therapy is now the standard of care for bladder cancer, especially in the post-TURBT setting [2][3][4][5][6][7][8][9][10]. The proposed mechanism of action for the attachment of live BCG proceeds via internalization into the abnormally proliferating transitional cells lining the bladder, causing an upregulation of gene expression, which leads to an increase in proinflammatory cytokine factors [3].…”

“…Microbial products for the treatment of cancer have been used since it was first proposed in the late 1800s by Dr. William B. Coley, and the idea of using Mycobacteria in the oncology context originated with Raymond Pearl, who observed decreased incidence of cancer lesions in patients with active tuberculosis [3]. BCG therapy as such was successfully applied for the first time in the late 1970s, and its use as a treatment modality for bladder cancer has substantially increased to a point where it has now become the standard of care [2][3][4][5][6][7]. Intravesical BCG therapy has been associated with decreased progression and risk of recurrence of the disease and compares favorably with intravesical chemotherapy in this respect [3].…”

“…BCG therapy as such was successfully applied for the first time in the late 1970s, and its use as a treatment modality for bladder cancer has substantially increased to a point where it has now become the standard of care [2][3][4][5][6][7]. Intravesical BCG therapy has been associated with decreased progression and risk of recurrence of the disease and compares favorably with intravesical chemotherapy in this respect [3]. Local and systemic complications have indeed been associated with it, although rarely, including (in descending order of prevalence) fever, hematuria, granulomatous prostatitis, pneumonitis and hepatitis, arthralgia, rash, ureteral obstruction, epididymitis, contracted bladder, renal abscess, sepsis, and cytopenia [7].…”