The Potential for Selective Cyclin-Dependent Kinase 4/6 Inhibition in the Therapy for Head and Neck Squamous Cell Carcinoma
Preclinical data support investigation of selective CDK4/6 inhibition as a therapeutic strategy for human papillomavirus (HPV)–unrelated head and neck squamous cell carcinoma (HNSCC). Phase 1 clinical trials established the feasibility of combining palbociclib with cetuximab in patients with recurrent or metastatic HNSCC. Nonrandomized phase II trials showed that palbociclib plus cetuximab resulted in efficacy outcomes better than cetuximab in biomarker-unselected, platinum-resistant or cetuximab-resistant, HPV-unrelated HNSCC. A double-blind, randomized phase II trial (PALATINUS) evaluated the efficacy of palbociclib or...
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
PI3K Inhibition for Squamous Cell Head and Neck Carcinoma
The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in most head and neck squamous cell carcinomas, making it a prized target for targeted therapy development. Multiple PI3K inhibitors have been studied in early phase trials, with unfavorable risk-benefit ratios in molecularly unselected patient populations. Buparlisib, a potent pan–class I PI3K inhibitor, shows promising efficacy in combination with paclitaxel for advanced head and neck squamous cell carcinoma. Results of the phase III BURAN trial are awaited. (Source: The Cancer Journal)
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Targeting HRAS in Head and Neck Cancer: Lessons From the Past and Future Promise
HRAS mutations define a unique biologic subset of head and neck squamous cell carcinoma. Oncogenic HRAS is uniquely dependent on posttranslational farnesylation for membrane localization and activation of downstream signaling. Tipifarnib, a farnesyltransferase inhibitor, demonstrated encouraging antitumor activity for HRAS mutant head and neck squamous cell carcinoma and modest activity for HRAS mutant salivary gland cancer. New combination strategies to circumvent intrinsic and acquired resistance to TFIs are being investigated. (Source: The Cancer Journal)
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Therapeutic Targeting of FGFR Signaling in Head and Neck Cancer
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most prevalent cancer worldwide, with an annual incidence of 600,000 new cases. Despite advances in surgery, chemotherapy, and radiotherapy, the overall survival for HNSCC patients has not been significantly improved over the past several decades. Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) genomic alterations are frequently detected in HNSCC, including amplification, activating mutation, and chromosomal rearrangement. Among them, FGFR1 amplification, FGF amplifications, and FGFR3 mutations are the most prevalent. In addition, FGF...
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
c-Met Signaling as a Therapeutic Target in Head and Neck Cancer
Despite a dearth of activating driver mutations in head and neck squamous cell carcinoma (HNSCC), aberrant activation of the oncogenes, epidermal growth factor receptor (EGFR), and c-Met is near-universal in human papillomavirus (HPV)–negative disease. Although EGFR activation drove the successful development of the anti-EGFR monoclonal antibody cetuximab in HNSCC, no c-Met–targeting therapy has gained regulatory approval. Inhibition of the c-Met pathway may subvert oncogenesis within the tumor-intrinsic compartment, blocking tumoral proliferation, invasion, migration, and metastasis, or the tumor-extrinsic compartment...
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
HER2 and HER3 as Therapeutic Targets in Head and Neck Cancer
Work over the past several decades has identified that aberrations in the ErbB signaling pathways are key drivers of oncogenesis, and concurrent efforts to discover targetable vulnerabilities to counter this aberrant oncogenic signaling offer tremendous promise in treating a host of human cancers. These efforts have been centered primarily on EGFR (also known as HER1), leading to the discovery of the first targeted therapies approved for head and neck cancer. More recently, HER2 and HER3 signaling pathways have been identified as highly dysregulated in head and neck cancer. This review highlights the HER2 and HER3 signalin...
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Targeting Epidermal Growth Factor Receptor in Head and Neck Cancer
Head and neck squamous cell carcinomas are rising in incidence worldwide, and despite the advent of improved surgical and radiation techniques, a substantial proportion of patients have disease recurrence, where systemic therapies are the mainstay of management. Recent advances in systemic therapy include the development of epidermal growth factor receptor– and programmed death 1–targeting drugs, which have produced incremental improvements in disease outcomes. However, for most patients, responses to treatment remain elusive because of primary or acquired resistance. Novel drugs and rational drug combinations need to ...
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Integrating Targeted Therapies in the Management of Head and Neck Cancers
No abstract available (Source: The Cancer Journal)
Source: The Cancer Journal - September 1, 2022 Category: Cancer & Oncology Tags: Introduction From the Guest Editor Source Type: research
Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy
Children and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing need for novel therapeutic strategies. Adoptive cellular therapy (ACT) has demonstrated activity in multiple adult cancer types, and opportunity exists to expand the use of this therapy in children. Employment of immunotherapy in the pediatric population has realized only modest overall clinical trial results, with success thus far restricted mainly to antibody-based therapies and chimeric antigen receptor T-cell therapies for lymphoid malignancy. As we improve our ...
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Current State of Cell Therapies for Gastrointestinal Cancers
Adoptive cell therapies include multiple cell-based therapies to harness the immune system's power to mount a robust anticancer effect. Early successes in solid tumors with checkpoint inhibition have increased the research and development of immunotherapy. The utilization of cell-based therapy for gastrointestinal malignancies is still in its infancy because of challenges of antigen specificity and access to the tumor microenvironment. In this review, we discuss the current state of adoptive cell therapies in terms of challenges and early successes in preclinical and clinical studies. (Source: The Cancer Journal)
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Current State of Cell Therapies for Breast Cancer
Metastatic breast cancer (BC) is an aggressive form of cancer and is an absolute challenge to treat. This review discusses the standard treatments available for metastatic BC. It further highlights the rationale for targeting oncodrivers, tumor-associated antigens, and neoantigens in BC. Explaining the significance of immune response in successful immunotherapeutic studies, it draws attention towards how adoptive cell therapy can be a useful immunotherapeutic tool. We focus on adoptive cell therapy in BC covering tumor-infiltrating lymphocyte therapy, engineered T cell receptor therapy, chimeric antigen receptor therapy, d...
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Current State of Cell Therapies for Genitourinary Malignancies
Genitourinary (GU) cancers have greatly benefited from immunotherapy treatments, such as immune checkpoint inhibitors. However, the durable clinical response rate for these agents remains relatively low, calling for more innovative immunotherapy approaches. Adoptive cell therapy has shown a significant advancement in the treatment of cancer in recent years and represents a great potential for the treatment of GU cancers. This review summarizes the current advancements in cellular therapy strategies for the treatment of renal cell carcinoma, bladder cancer, and prostate and penile cancers. Further, current and past clinical...
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Surgical Considerations for Tumor Tissue Procurement to Obtain Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy
Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), an investigational cellular therapy, has demonstrated antitumor efficacy in patients with advanced solid tumors, including melanoma. Tumor-infiltrating lymphocyte cell therapy involves surgical resection of a patient's tumor, ex vivo TIL expansion under conditions that overcome immunosuppressive responses elicited by the tumor and the tumor microenvironment, administration of a lymphodepleting regimen, and infusion of the final TIL cell therapy product back into the patient followed by interleukin 2 administration to support T-cell activity. The surgeon play...
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
Neoantigen-Specific T Cells in Adoptive Cell Therapy
This article reviews the clinical application of adoptive cell therapy targeting neoantigens in patients with epithelial cancers. (Source: The Cancer Journal)
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
γδ T Cell–Based Adoptive Cell Therapies Against Solid Epithelial Tumors
Conventionally, adoptive cell therapies have been developed and optimized using αβ T cells. However, the understudied and less abundant γδ T cells offer unique advantages to the immunotherapy field especially for therapies against solid tumors. Recently, γδ T-cell potential against a broad spectrum of malignant cells has been demonstrated in the preclinical setting. In the clinic, γδ T-cell–based immunotherapies have proven to be safe; however, their efficacy needs improvement. Considering the growing body of literature reflecting the increasing interest in γδ T cells, we sought to capture the current topics of...
Source: The Cancer Journal - July 1, 2022 Category: Cancer & Oncology Tags: Review Articles Source Type: research
