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In carcinogenesis of the gastrointestinal (GI) tract, the deregulation of fibroblast growth factor receptor (FGFR) signaling plays a critical role. The aberrant activity of this pathway is described in approximately 10% of gastric cancers and its frequency increases in intrahepatic cholangiocarcinomas (iCCAs), with an estimated frequency of 10–16%. Several selective FGFR inhibitors have been developed in the last few years with promising results. For example, targeting the FGFR pathway is now a fundamental part of clinical practice when treating iCCA and many clinical trials are ongoing to test the safety and efficacy of anti-FGFR agents in gastric, colon and pancreatic cancer, with variable results. However, the response rates of anti-FGFR drugs are modest and resistances emerge rapidly, limiting their efficacy and causing disease progression. In this review, we aim to explore the landscape of anti-FGFR inhibitors in relation to GI cancer, with particular focus on selective FGFR inhibitors and drug combinations that may lead to overcoming resistance mechanisms and drug-induced toxicities. [ABSTRACT FROM AUTHOR]

Vaccines are a promising therapeutic alternative to monoclonal antibodies against HER-2+ breast cancer. We present the preclinical activity of an ES2B-C001, a VLP-based vaccine being developed for human breast cancer therapy. FVB mice challenged with HER-2+ mammary carcinoma cells QD developed progressive tumors, whereas all mice vaccinated with ES2B-C001+Montanide ISA 51, and 70% of mice vaccinated without adjuvant, remained tumor-free. ES2B-C001 completely inhibited lung metastases in mice challenged intravenously. HER-2 transgenic Delta16 mice developed mammary carcinomas by 4–8 months of age; two administrations of ES2B-C001+Montanide prevented tumor onset for >1 year. Young Delta16 mice challenged intravenously with QD cells developed a mean of 68 lung nodules in 13 weeks, whereas all mice vaccinated with ES2B-C001+Montanide, and 73% of mice vaccinated without adjuvant, remained metastasis-free. ES2B-C001 in adjuvant elicited strong anti-HER-2 antibody responses comprising all Ig isotypes; titers ranging from 1–10 mg/mL persisted for many months. Antibodies inhibited the 3D growth of human HER-2+ trastuzumab-sensitive and -resistant breast cancer cells. Vaccination did not induce cytokine storms; however, it increased the ELISpot frequency of IFN-γ secreting HER-2-specific splenocytes. ES2B-C001 is a promising candidate vaccine for the therapy of tumors expressing HER-2. Preclinical results warrant further development towards human clinical studies. [ABSTRACT FROM AUTHOR]

In carcinogenesis of the gastrointestinal (GI) tract, the deregulation of fibroblast growth factor receptor (FGFR) signaling plays a critical role. The aberrant activity of this pathway is described in approximately 10% of gastric cancers and its frequency increases in intrahepatic cholangiocarcinomas (iCCAs), with an estimated frequency of 10–16%. Several selective FGFR inhibitors have been developed in the last few years with promising results. For example, targeting the FGFR pathway is now a fundamental part of clinical practice when treating iCCA and many clinical trials are ongoing to test the safety and efficacy of anti-FGFR agents in gastric, colon and pancreatic cancer, with variable results. However, the response rates of anti-FGFR drugs are modest and resistances emerge rapidly, limiting their efficacy and causing disease progression. In this review, we aim to explore the landscape of anti-FGFR inhibitors in relation to GI cancer, with particular focus on selective FGFR inhibitors and drug combinations that may lead to overcoming resistance mechanisms and drug-induced toxicities.

Bullous pemphigoid is a subepidermal blistering disease associated with autoantibodies (auto-ab) to BP180 and BP230 which affects elderly patients, predominately. Although it is a rare disease, bullous pemphigoid is the most common among the autoimmune bullous skin diseases. Systemic corticosteroids and immunosuppressants represent milestones in the treatment of patients suffering from bullous pemphigoid; however, therapeutic management of patients still represents a clinical challenge, owing to the chronic nature of the disease and to potential adverse effects related to the long-term use of systemic treatments. Recent discoveries on the pathogenesis of bullous pemphigoid have allowed investigation of new target therapies against selective pro-inflammatory mediators. These therapies appear to yield satisfactory results with fewer side effects in cases of refractory disease. The review discusses current evidence on these new therapeutic targets and specific drugs under investigation.

Vaccines are a promising therapeutic alternative to monoclonal antibodies against HER-2+ breast cancer. We present the preclinical activity of an ES2B-C001, a VLP-based vaccine being developed for human breast cancer therapy. FVB mice challenged with HER-2+ mammary carcinoma cells QD developed progressive tumors, whereas all mice vaccinated with ES2B-C001+Montanide ISA 51, and 70% of mice vaccinated without adjuvant, remained tumor-free. ES2B-C001 completely inhibited lung metastases in mice challenged intravenously. HER-2 transgenic Delta16 mice developed mammary carcinomas by 4–8 months of age; two administrations of ES2B-C001+Montanide prevented tumor onset for >1 year. Young Delta16 mice challenged intravenously with QD cells developed a mean of 68 lung nodules in 13 weeks, whereas all mice vaccinated with ES2B-C001+Montanide, and 73% of mice vaccinated without adjuvant, remained metastasis-free. ES2B-C001 in adjuvant elicited strong anti-HER-2 antibody responses comprising all Ig isotypes; titers ranging from 1–10 mg/mL persisted for many months. Antibodies inhibited the 3D growth of human HER-2+ trastuzumab-sensitive and -resistant breast cancer cells. Vaccination did not induce cytokine storms; however, it increased the ELISpot frequency of IFN-γ secreting HER-2-specific splenocytes. ES2B-C001 is a promising candidate vaccine for the therapy of tumors expressing HER-2. Preclinical results warrant further development towards human clinical studies.

Renal cell carcinoma (RCC) is an increasingly common malignancy that can progress to metastatic renal cell carcinoma (mRCC) in approximately one-third of RCC patients. The 5-year survival rate for mRCC is abysmally low, and, at the present time, there are sparingly few if any effective treatments. Current surgical and pharmacological treatments can have a long-lasting impact on renal function, as well. Thus, there is a compelling unmet need to discover novel biomarkers and surveillance methods to improve patient outcomes with more targeted therapies earlier in the course of the disease. Circulating biomarkers, such as circulating tumor DNA, noncoding RNA, proteins, extracellular vesicles, or cancer cells themselves potentially represent a minimally invasive tool to fill this gap and accelerate both diagnosis and treatment. Here, we discuss the clinical relevance of different circulating biomarkers in metastatic renal cell carcinoma by clarifying their potential role as novel biomarkers of response or resistance to treatments but also by guiding clinicians in novel therapeutic approaches.

Bullous pemphigoid is a subepidermal blistering disease associated with autoantibodies (auto-ab) to BP180 and BP230 which affects elderly patients, predominately. Although it is a rare disease, bullous pemphigoid is the most common among the autoimmune bullous skin diseases. Systemic corticosteroids and immunosuppressants represent milestones in the treatment of patients suffering from bullous pemphigoid; however, therapeutic management of patients still represents a clinical challenge, owing to the chronic nature of the disease and to potential adverse effects related to the long-term use of systemic treatments. Recent discoveries on the pathogenesis of bullous pemphigoid have allowed investigation of new target therapies against selective pro-inflammatory mediators. These therapies appear to yield satisfactory results with fewer side effects in cases of refractory disease. The review discusses current evidence on these new therapeutic targets and specific drugs under investigation.

Renal cell carcinoma (RCC) is an increasingly common malignancy that can progress to metastatic renal cell carcinoma (mRCC) in approximately one-third of RCC patients. The 5-year survival rate for mRCC is abysmally low, and, at the present time, there are sparingly few if any effective treatments. Current surgical and pharmacological treatments can have a long-lasting impact on renal function, as well. Thus, there is a compelling unmet need to discover novel biomarkers and surveillance methods to improve patient outcomes with more targeted therapies earlier in the course of the disease. Circulating biomarkers, such as circulating tumor DNA, noncoding RNA, proteins, extracellular vesicles, or cancer cells themselves potentially represent a minimally invasive tool to fill this gap and accelerate both diagnosis and treatment. Here, we discuss the clinical relevance of different circulating biomarkers in metastatic renal cell carcinoma by clarifying their potential role as novel biomarkers of response or resistance to treatments but also by guiding clinicians in novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is an increasingly common malignancy that can progress to metastatic renal cell carcinoma (mRCC) in approximately one-third of RCC patients. The 5-year survival rate for mRCC is abysmally low, and, at the present time, there are sparingly few if any effective treatments. Current surgical and pharmacological treatments can have a long-lasting impact on renal function, as well. Thus, there is a compelling unmet need to discover novel biomarkers and surveillance methods to improve patient outcomes with more targeted therapies earlier in the course of the disease. Circulating biomarkers, such as circulating tumor DNA, noncoding RNA, proteins, extracellular vesicles, or cancer cells themselves potentially represent a minimally invasive tool to fill this gap and accelerate both diagnosis and treatment. Here, we discuss the clinical relevance of different circulating biomarkers in metastatic renal cell carcinoma by clarifying their potential role as novel biomarkers of response or resistance to treatments but also by guiding clinicians in novel therapeutic approaches.