A Phase 2 Trial of Afatinib in Patients with Solid Tumors that Harbor Genomic Aberrations in the HER family: The MOBILITY3 Basket Study

Salawu, Abdulazeez; Hansen, Aaron Richard; Spreafico, Anna; Al-Ezzi, Esmail Mutahar; Webster, Sheila; Bédard, Philippe L.; Doi, Jeffrey; Wang, Lisa; Siu, Lillian L.; Razak, Albiruni R. Abdul

doi:10.1007/s11523-022-00884-z

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…In one of them, the study group detected synchronous TP53 and ERBB2 mutations in a series of oncocytic SGCs, which represent a distinct histopathologically and molecularly heterogenous group inside the SGC super family (34). Similarly, another genetic analysis showed differences in ERBB2 mutation/amplification status regarding a series of solid malignancies analyzed, including SGCs (35). Finally, two more genes, the catenin beta 1 gene (CTTNB1: 3p22) encoding a significant cell-to-cell adhesion molecule acting as a cadherin-associated factor, and CYLD lysine 63 deubiquitinase (CYLD: 16q12) gene, encoding a strong protease, have been found to be mutated in tubulotrabecular basal cell and membranous basal cell adenomas and adenocarcinomas of salivary glands (36,37).…”

Section: Cancer Diagnosis and Prognosismentioning

confidence: 92%

Mutational Signatures in Salivary Gland Carcinomas

Chrysovergis¹,

Papanikolaou²,

Spyropoulou³

et al. 2023

CDP

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Salivary gland carcinomas belong to the head and neck carcinoma super category of malignancies. They are characterized by histopathological diversity and comprise a variety of entities and subtypes. Mucoepidermoid, adenoid cystic and salivary duct carcinomas represent the most prominent malignancies. Concerning their corresponding genetic background, a broad spectrum of gene and chromosomal imbalances has been detected. Point mutations and deletions, amplifications and translocations, combined or not with chromosomal aneuploidy/polysomy/monosomy, create a landscape of specific genetic signatures that affect the biological behavior of these tumors and modify response rates to potential targeted therapeutic strategies. In the current molecular review, we focused on the categorization and description of the most important mutational signatures in salivary gland carcinomas.

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Section: Cancer Diagnosis and Prognosismentioning

confidence: 92%

Mutational Signatures in Salivary Gland Carcinomas

Chrysovergis¹,

Papanikolaou²,

Spyropoulou³

et al. 2023

CDP

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“…For example, afatinib has shown clinical efficacy against lung cancers harboring exon 19 deletions, L858R substitutions, or some other EGFR activating mutations located in exons 18-21 of the EGFR gene [9]. Consequently, the attempt to use it against tumors with EGFR exon 13 R521K mutations appears to be poorly justified [141]. Of note, the same study demonstrated a clinical benefit from this drug in a patient with an EGFR L858R-mutated salivary gland tumor [141].…”

Section: Agnostic Administration Of Anticancer Drugs Based On the Res...mentioning

confidence: 99%

“…Consequently, the attempt to use it against tumors with EGFR exon 13 R521K mutations appears to be poorly justified [141]. Of note, the same study demonstrated a clinical benefit from this drug in a patient with an EGFR L858R-mutated salivary gland tumor [141]. Afatinib has shown no benefit in patients with HER2-mutated lung carcinomas [142].…”

Section: Agnostic Administration Of Anticancer Drugs Based On the Res...mentioning

confidence: 99%

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution

Aleksakhina,

Ivantsov,

Imyanitov

2024

IJMS

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Many tumors have well-defined vulnerabilities, thus potentially allowing highly specific and effective treatment. There is a spectrum of actionable genetic alterations which are shared across various tumor types and, therefore, can be targeted by a given drug irrespective of tumor histology. Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. Multiple lines of evidence suggest that this histology-independent approach is also reasonable for tumors carrying ALK and ROS1 translocations, biallelic BRCA1/2 inactivation and/or homologous recombination deficiency (HRD), strong HER2 amplification/overexpression coupled with the absence of other MAPK pathway-activating mutations, etc. On the other hand, some well-known targets are not agnostic: for example, PD-L1 expression is predictive for the efficacy of PD-L1/PD1 inhibitors only in some but not all cancer types. Unfortunately, the individual probability of finding a druggable target in a given tumor is relatively low, even with the use of comprehensive next-generation sequencing (NGS) assays. Nevertheless, the rapidly growing utilization of NGS will significantly increase the number of patients with highly unusual or exceptionally rare tumor-target combinations. Clinical trials may provide only a framework for treatment attitudes, while the decisions for individual patients usually require case-by-case consideration of the probability of deriving benefit from agnostic versus standard therapy, drug availability, associated costs, and other circumstances. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.

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“…The outcome and biocompatibility of HER2-based CAR-T therapy have been investigated in trials in HER2-positive sarcoma, and dose-limiting toxicity has not been observed. [352][353][354] Although it is expressed at a lower level, HER2 can also be efficiently recognized by CAR-T lymphocytes, suggesting that CAR-T cells have great potential to target cancer cells. By using an osteosarcoma mouse model, researchers found that metastatic cancer cells that were insensitive to chemotherapeutic agents could be efficiently eliminated by the IL-11 receptor α-chain (IL-11Rα) and CAR-T cells modified to target HER2.…”

Section: Immune Checkpoint Blockade-based Immunotherapy For Osteosarcomamentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

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A Phase 2 Trial of Afatinib in Patients with Solid Tumors that Harbor Genomic Aberrations in the HER family: The MOBILITY3 Basket Study

Cited by 6 publications

References 47 publications

Mutational Signatures in Salivary Gland Carcinomas

Mutational Signatures in Salivary Gland Carcinomas

Agnostic Administration of Targeted Anticancer Drugs: Looking for a Balance between Hype and Caution

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

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