Treatment of Fanconi Anemia–Associated Head and Neck Cancer: Opportunities to Improve Outcomes

Lee, Rex H.; Kang, Hyunseok; Yom, Sue S.; Smogorzewska, Agata; Johnson, Daniel; Grandis, Jennifer R.

doi:10.1158/1078-0432.ccr-21-1259

Cited by 9 publications

References 116 publications

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“…Targeted chemo-therapy (such as cetuximab or gefitinib) or immuno-therapy (e.g., nivolumab, pembrolizumab) are definitely intriguing, but their actual efficacy and complication rates have still to be assessed overall [ 37 ]. It follows that the first-line therapeutic strategy is surgery.…”

Section: Discussionmentioning

confidence: 99%

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Tongue cancer following hematopoietic cell transplantation for Fanconi anemia

Bartolomeo

Anesi²,

Pellacani³

et al. 2022

Clin Oral Invest

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Objectives The aim of this retrospective study was to determine the incidence and the clinical outcome of tongue cancer (TC) in patients affected by Fanconi anemia (FA) who received an allogeneic hematopoietic cell transplantation (HCT). Materials and methods The patient database from the Bone Marrow Transplant Center of Pescara was reviewed to enroll FA patients. Patients’, donors’, HCT’s, and screening’s data were collected as well to look for the incidence and the treatment of TC. Results Twelve patients affected by FA were identified. Three patients died for transplant-related causes. Five of nine surviving patients were diagnosed with TC at a median of 21.7 years since transplantation and at a median age of 32.10 years. Interestingly, no patient manifested graft-versus-host-disease (GvHD). The 28-year cumulative incidence function of TC was 46.9% (95% CI, 36.9–56.9%). Two patients were treated with chemotherapy alone, two patients were treated with surgery alone, and one with surgery followed by chemotherapy. Overall, 4 patients with TC showed a clinical course characterized by a marked aggressiveness of the tumor disease which led to death due to cancer progression between 2 and 13 months. One patient is surviving 8 months after diagnosis of TC. Conclusions Our study confirms the high incidence of tumors and in particular tongue tumors in allotransplanted FA patients. A careful screening has to be life-long maintained. Clinical relevance Considering the rarity of FA and the frailty of FA patients, this study may add important information for the cancer management of these patients.

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Section: Discussionmentioning

confidence: 99%

“…It follows that the first-line therapeutic strategy is surgery. As demonstrated by Lee, patients with FA can also undergo major surgery without developing particular complications [ 37 ]. Conspicuous resective interventions are also possible, associated with reconstructive surgery which may include free flaps as well.…”

Section: Discussionmentioning

confidence: 99%

Tongue cancer following hematopoietic cell transplantation for Fanconi anemia

Bartolomeo

Anesi²,

Pellacani³

et al. 2022

Clin Oral Invest

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“…However, some reports suggest that HPV may be a major contributor to HNSCC development in patients with FA 3 , whereas other studies dispute these results 4 . HNSCC in FA is difficult to treat, as patients cannot tolerate current therapies, including ionizing radiation or DNA cross-linking, platinum-based chemotherapies 5 . In addition, most tumors are detected at advanced stages.…”

Section: Introductionmentioning

confidence: 99%

Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia

Errazquin

Page

Segrelles

et al. 2022

Preprint

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Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA is diagnosed within the first 3-4 decades of life, and patients respond poorly to current treatments, mainly radiotherapy and chemotherapy. In addition, FA patients develop oral lesions very often that might precede malignant transformation. Research and translation of new chemopreventive and therapeutic strategies has been unsuccessful in part because disease models are scarce or do not fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca-/-) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of p53 gene in oral mucosa (K14cre;Trp53F2-10/F2-10) spontaneously develop OSCC with high penetrance and a median latency of less than ten months. Tumors are well differentiated and express markers of squamous differentiation, such as K5 and K10 keratins. In conclusion, Fanca and p53 genes cooperate to suppress oral cancer in mice, and Fanca-/-;K14cre;Trp53F2-10/F2-10 constitute the first animal model of spontaneous OSCC in FA.

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“…Multiple oral cavity carcinomas are distressingly common (3), and an elevated risk of cutaneous squamous carcinomas has been documented together with a continuing, elevated risk of leukemia (3,4). However, SCC may be the first clinical presentation of FA at any age (1,5). Many other cancer types have been reported in individuals with FA, but only a small subset - liver and brain tumors, lymphomas, and embryonal tumors such as Wilms tumor and neuroblastoma - are observed at higher-than-expected frequencies versus population controls (3), and none with risk estimates approaching those of squamous mucosal carcinomas.…”

Section: Introductionmentioning

confidence: 99%

“…Effective therapies for FA-associated SCC have also proven elusive: many cancers are detected too late for surgical cure, and FA patients cannot tolerate effective doses of standard-of-care therapies including DNA cross-linking drugs and ionizing radiation (5). These features of cancer in FA - the often-late clinical recognition, synchronous or metasynchronous tumors and therapeutic intractability - have collectively made SCC the leading cause of premature morbidity and mortality in adults with FA.…”

Section: Introductionmentioning

confidence: 99%

Fanconi anemia-isogenic head and neck cancer cell line pairs - a basic and translational science resource

Nguyen

Tang

Webster

et al. 2022

Preprint

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Fanconi anemia (FA) is a heritable malformation, bone marrow failure and cancer predisposition syndrome that confers an exceptionally high risk of developing carcinomas arising in squamous mucosal epithelia lining the mouth, proximal esophagus, vulva and anus. The origin of these cancers is not understood, and no effective way has been identified to prevent or delay their appearance. FA-associated carcinomas are also therapeutically challenging, as they may be multi-focal and stage-advanced at diagnosis making surgical control challenging. Moreover, individuals with FA have systemic DNA damage hypersensitivity and thus an elevated risk of toxicity when treated with standard-of-care therapies such as DNA cross-linking drugs and ionizing radiation. We developed the Fanconi Anemia Cancer Cell Line Resource (FA-CCLR) in order to foster new research on the origins, treatment, and prevention of FA-associated cancers. The FA-CCLR consists of FANC-isogenic head and neck squamous cell carcinoma (HNSCC) cell line pairs from cancers arising in individuals with FA, or newly engineered from sporadic HNSCC cell lines. Molecular, cellular, and biochemical analyses were used to demonstrate the causal dependence of key FA-associated phenotypes on FANC genotype, expression and pathway activity. These FANC-isogenic cell line pairs are available to academic and non-profit investigators, with ordering information available at the Fanconi Anemia Research Materials Resource and Repository at Oregon Health & Sciences University, Portland OR.

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Treatment of Fanconi Anemia–Associated Head and Neck Cancer: Opportunities to Improve Outcomes

Cited by 9 publications

References 116 publications

Tongue cancer following hematopoietic cell transplantation for Fanconi anemia

Tongue cancer following hematopoietic cell transplantation for Fanconi anemia

Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia

Fanconi anemia-isogenic head and neck cancer cell line pairs - a basic and translational science resource

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