Head & Neck Cancers, FGFR1

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Expand Collapse Head & Neck Cancers  - General Description This year about 52,000 people in the U.S. will be told by a doctor that they have cancer of the head and neck. Approximately 70% of these new patients will be men. However, about 265,000 Americans remain alive today after having been diagnosed with head & neck cancer.

Head and neck cancers develop inside the mouth (in the oral cavity), nose (nasal cavity), or the tube (pharynx) that runs from the back of the nose to the top of the windpipe (trachea) and the top of the tube that goes to the stomach (esophagus). Cancers that begins in the lips, salivary glands, throat or voice box (larynx) are also classified as head and neck cancer. However, cancers of the esophagus, eye, brain, and thyroid gland usually aren't regarded as head and neck cancers, and neither are cancers of the skin, muscles, or bones of the head and neck. Head and neck cancers usually begin in squamous cells and therefore are called squamous cell carcinomas. The FDA has approved the targeted therapy cetuximab (Erbitux) for treatment of patients with squamous cell carcinoma of the head and neck.

Head and neck cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging can also be performed to determine if the cancer has spread. These include MRI and CT scans.

Despite significant improvements in the treatment of head & neck cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
An estimated 644,000 new cases of head and neck cancer are diagnosed each year worldwide, posing the sixth leading cause of cancer death. The American Cancer Society projected 39,400 new head and neck cancer diagnoses and 7,900 cancer deaths in the U.S. in 2009. In Europe, the projected incidence for 2008 was 132,300 and the mortality was 62,800. The estimated annual incidence of head and neck cancers is 2-4-fold higher among men than women.

More than 95% of head and neck cancers are of squamous cell histology (SCCHN) and originate in the mucosal lining of the upper aerodigestive tract. Anatomic sites include the lip/oral cavity, nasopharynx, oropharynx, hypopharynx and larynx. Common risk factors include tobacco use (smoking and/or chewing) and alcohol consumption, with a suggested synergistic effect. Less common risk factors include chewing of betel nuts (a common practice in some parts of Asia) and occupational exposures. Infection with the oncogenic human papillomavirus (HPV) has been identified as a distinct and rising risk factor, particularly among patients with squamous cell carcinoma of the oropharynx, specifically tonsils and the base of tongue. The incidence of SCCHN has increased steadily during the last several decades, whereas the incidence of tobacco-associated SCCHN has decreased, to the point where the incidence of HPV-associated and non-HPV-associated cancers is nearly equivalent. HPV status has been shown to strongly predict outcomes in patients with locally or regionally advanced oropharynx squamous cell carcinoma, but the prognostic impact of HPV in recurrent/metastatic SCCHN is currently less well understood.

Molecular hallmarks of SCCHN that have been identified as key drivers over the past decade include gene mutations in TP53, CDKN2A, PIK3CA, PTEN and HRAS. Recent investigations using high-throughput gene sequencing also found mutations in other cell differentiation-related genes, such as NOTCH1, NOTCH2, NOTCH3 and TP63, suggesting that deregulation of the terminal differentiation program is critical for squamous cancer development.

The epidermal growth factor receptor (EGFR) and its downstream molecular pathways are of particular importance in SCCHN. EGFR is overexpressed in up to 90% of all SCCHN. High expression levels of EGFR and transforming growth factor (TGF, a ligand of EGFR), as well as EGFR gene amplification, has been associated with increased resistance to treatment and poorer clinical outcome, including decreased disease-free and overall survival.

Therapeutic options and treatment decisions at first diagnosis are dependent on disease stage. For early-stage and locally advanced disease (the majority of new
cases), therapy is tailored to the primary site of disease, feasibility of organ preservation and prognosis and functional outcomes following therapy. Despite aggressive treatment, only 35% to 55% of patients who present with locally advanced SCCHN remain alive and free of disease 3 years after standard curative treatment. Between 30-40% of patients develop loco-regional recurrences, with distant metastases occurring in 20-30% of cases. The majority of recurrences appear within 2 years of initial treatment. An additional 10-20% of patients have evidence of distant metastases at the time of first diagnosis.

For patients with recurrent/metastatic SCCHN who are considered incurable with surgery or radiotherapy, first-line palliative treatment options include platinum agents, taxanes, methotrexate, 5-fluorouracil and cetuximab. Even with combination regimens, objective radiographic responses are achieved in fewer than 40% of patients in most large studies. Patients with disease progression on platinum-based therapy have limited treatment options and a poor prognosis. In these patients, overall response to second-line cytotoxic therapy has been 3%. Poor survival at this stage is related to the development of metastases and poor local disease control.

Source: National Cancer Institute, 2012
This year about 52,000 people in the U.S. will be told by a doctor that they have cancer of the head and neck. Approximately 70% of these new patients will be men. However, about 265,000 Americans remain alive today after having been diagnosed with head & neck cancer.

Head and neck cancers develop inside the mouth (in the oral cavity), nose (nasal cavity), or the tube (pharynx) that runs from the back of the nose to the top of the windpipe (trachea) and the top of the tube that goes to the stomach (esophagus). Cancers that begins in the lips, salivary glands, throat or voice box (larynx) are also classified as head and neck cancer. However, cancers of the esophagus, eye, brain, and thyroid gland usually aren't regarded as head and neck cancers, and neither are cancers of the skin, muscles, or bones of the head and neck. Head and neck cancers usually begin in squamous cells and therefore are called squamous cell carcinomas. The FDA has approved the targeted therapy cetuximab (Erbitux) for treatment of patients with squamous cell carcinoma of the head and neck.

Head and neck cancer (and other tumors) can spread (metastasize) from the place where it started (the primary tumor) in 3 ways. First, it can invade the normal tissue surrounding it. Second, cancer cells can enter the lymph system and travel through lymph vessels to distant parts of the body. Third, the cancer cells can get into the bloodstream and go to other places in the body. In these distant places, the cancer cells cause secondary tumors to grow. To find out whether the cancer has entered the lymph system, a surgeon removes all or part of a node near the primary tumor and a pathologist looks at it through a microscope to see if cancer cells are present. Several kinds of imaging can also be performed to determine if the cancer has spread. These include MRI and CT scans.

Despite significant improvements in the treatment of head & neck cancers, novel therapies and treatment strategies are needed.

Source: National Cancer Institute, 2012
An estimated 644,000 new cases of head and neck cancer are diagnosed each year worldwide, posing the sixth leading cause of cancer death. The American Cancer Society projected 39,400 new head and neck cancer diagnoses and 7,900 cancer deaths in the U.S. in 2009. In Europe, the projected incidence for 2008 was 132,300 and the mortality was 62,800. The estimated annual incidence of head and neck cancers is 2-4-fold higher among men than women.

More than 95% of head and neck cancers are of squamous cell histology (SCCHN) and originate in the mucosal lining of the upper aerodigestive tract. Anatomic sites include the lip/oral cavity, nasopharynx, oropharynx, hypopharynx and larynx. Common risk factors include tobacco use (smoking and/or chewing) and alcohol consumption, with a suggested synergistic effect. Less common risk factors include chewing of betel nuts (a common practice in some parts of Asia) and occupational exposures. Infection with the oncogenic human papillomavirus (HPV) has been identified as a distinct and rising risk factor, particularly among patients with squamous cell carcinoma of the oropharynx, specifically tonsils and the base of tongue. The incidence of SCCHN has increased steadily during the last several decades, whereas the incidence of tobacco-associated SCCHN has decreased, to the point where the incidence of HPV-associated and non-HPV-associated cancers is nearly equivalent. HPV status has been shown to strongly predict outcomes in patients with locally or regionally advanced oropharynx squamous cell carcinoma, but the prognostic impact of HPV in recurrent/metastatic SCCHN is currently less well understood.

Molecular hallmarks of SCCHN that have been identified as key drivers over the past decade include gene mutations in TP53, CDKN2A, PIK3CA, PTEN and HRAS. Recent investigations using high-throughput gene sequencing also found mutations in other cell differentiation-related genes, such as NOTCH1, NOTCH2, NOTCH3 and TP63, suggesting that deregulation of the terminal differentiation program is critical for squamous cancer development.

The epidermal growth factor receptor (EGFR) and its downstream molecular pathways are of particular importance in SCCHN. EGFR is overexpressed in up to 90% of all SCCHN. High expression levels of EGFR and transforming growth factor (TGF, a ligand of EGFR), as well as EGFR gene amplification, has been associated with increased resistance to treatment and poorer clinical outcome, including decreased disease-free and overall survival.

Therapeutic options and treatment decisions at first diagnosis are dependent on disease stage. For early-stage and locally advanced disease (the majority of new
cases), therapy is tailored to the primary site of disease, feasibility of organ preservation and prognosis and functional outcomes following therapy. Despite aggressive treatment, only 35% to 55% of patients who present with locally advanced SCCHN remain alive and free of disease 3 years after standard curative treatment. Between 30-40% of patients develop loco-regional recurrences, with distant metastases occurring in 20-30% of cases. The majority of recurrences appear within 2 years of initial treatment. An additional 10-20% of patients have evidence of distant metastases at the time of first diagnosis.

For patients with recurrent/metastatic SCCHN who are considered incurable with surgery or radiotherapy, first-line palliative treatment options include platinum agents, taxanes, methotrexate, 5-fluorouracil and cetuximab. Even with combination regimens, objective radiographic responses are achieved in fewer than 40% of patients in most large studies. Patients with disease progression on platinum-based therapy have limited treatment options and a poor prognosis. In these patients, overall response to second-line cytotoxic therapy has been 3%. Poor survival at this stage is related to the development of metastases and poor local disease control.

Source: National Cancer Institute, 2012
Expand Collapse FGFR1  - General Description
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FGFR1 is a gene that provides the code for making a cell surface protein called fibroblast growth factor receptor 1 (FGFR1). When bound to specific growth factors (proteins that stimulate cell growth and division), it activate a signaling system inside the cell that ultimately controls diverse functions such as the development of the nervous system and regulation of large bone growth.

In certain types of stomach and prostate cancers, there is an excess of FGFR1 produced in the cancer cells (overexpression). The excessive signaling that results from the extra receptors may make it easier for the cancer cells to grow, divide, and move. Unusual expression of the FGFR1 gene is also found in certain pancreatic, esophageal, ovarian, testicular, breast and head and neck cancers.

Source: Genetics Home Reference
FGFR1 is a gene that provides the code for making a protein called fibroblast growth factor receptor 1. This receptor is located on the surface of cells. When certain growth factors (proteins that stimulate cell growth and division) come into contact with (bind to) this receptor, they activate a signaling system within the cell that tells it to undergo certain changes. In its normal role, the FGFR1 protein is believed to help the nervous system develop, and it also may help regulate the growth of long bones.

In certain types of stomach and prostate cancers, the FGFR1 gene makes too make of the receptor (overexpression). The excessive signaling that results from the extra receptors may make it easier for the cancer cells to grow, divide and move. Unusual expression of the FGFR1 gene is also found in certain pancreatic, esophageal, ovarian, testicular, breast and head and neck cancers.

Source: Genetics Home Reference
Expand Collapse FGFR1  in Head & Neck Cancers
Preclinical studies clearly demonstrate that FGFR1 amplification confers dependence upon FGFR signaling. In multiple preclinical models, treatment of FGFR1-amplified cancer with selective FGFR kinase inhibitors resulted in growth inhibition and tumor reduction. It is still unknown whether FGFR1 amplification will confer sensitivity to FGFR inhibitors in head and neck cancer patients. Clinical trials with FGFR inhibitors are currently underway.

The FGFR1 gene is amplified in about 10% of head and neck squamous cell carcinoma cases.

Preclinical studies clearly demonstrate that FGFR1 amplification confers dependence upon FGFR signaling. In multiple preclinical models, treatment of FGFR1-amplified cancer with selective FGFR kinase inhibitors resulted in growth inhibition and tumor reduction. It is still unknown whether FGFR1 amplification will confer sensitivity to FGFR inhibitors in head and neck cancer patients. Clinical trials with FGFR inhibitors are currently underway.

The FGFR1 gene is amplified in about 10% of head and neck squamous cell carcinoma cases.

PubMed ID's
23418312
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The mutation of a gene provides clinicians with a very detailed look at your cancer. Knowing this information could change the course of your care. To learn how you can find out more about genetic testing please visit http://www.massgeneral.org/cancer/news/faq.aspx or contact the Cancer Center.
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Your Matched Clinical Trials

Trial Matches: (D) - Disease, (G) - Gene
Trial Status: Showing Results: 1-10 of 18 Per Page:
12Next »
Protocol # Title Location Status Match
NCT01948297 Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations Debio 1347-101 Phase I Trial in Advanced Solid Tumours With Fibroblast Growth Factor Receptor (FGFR) Alterations MGH Open DG
NCT02099058 A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors A Phase 1/1b Study With ABBV-399, an Antibody Drug Conjugate, in Subjects With Advanced Solid Cancer Tumors MGH Open D
NCT02365662 A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor MGH Open D
NCT01714739 A Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors A Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors MGH Open D
NCT02467361 A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers MGH Open D
NCT02471846 A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors MGH Open D
NCT02082210 A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer A Study of LY2875358 in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer MGH Open D
NCT00585195 A Study Of Oral PF-02341066, A c-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer A Study Of Oral PF-02341066, A c-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer MGH Open D
NCT01953926 An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification An Open-label, Phase 2 Study of Neratinib in Patients With Solid Tumors With Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification MGH Open D
NCT02568267 Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions) MGH Open D
Trial Status: Showing Results: 1-10 of 18 Per Page:
12Next »
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