A Review of HER2-Targeted Therapy in Breast and Ovarian Cancer: Lessons from Antiquity – CLEOPATRA and PENELOPE

Hodeib, Melissa; Serna-Gallegos, Tasha; Tewari, Krishnansu S.

doi:10.2217/fon.15.266

Cited by 20 publications

(14 citation statements)

References 72 publications

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“… 28 In ovarian cancer, low HER3 mRNA levels represented a more sensitive phenotype for the HER2 dimerization blocking mAb pertuzumab and gemcitabine treatment. 29 Identification of tumor HER3 levels and heterogeneity might therefore pose an attractive option for patient stratification. The highly specific tumor uptake in our study indicates that changes and variation in HER3 expression might be sensitively assessed using a humanized version of 89 Zr-mAb3481 for HER3 PET.…”

Section: Discussionmentioning

confidence: 99%

⁸⁹Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

Pool

Kol

Jong

et al. 2017

mAbs

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Treatment of human epidermal growth factor receptor 2 (HER2)-driven breast cancer with tyrosine kinase inhibitor lapatinib can induce a compensatory HER3 increase, which may attenuate antitumor efficacy. Therefore, we explored in vivo HER3 tumor status assessment after lapatinib treatment with zirconium-89 (89Zr)-labeled anti-HER3 antibody mAb3481 positron emission tomography (PET). Lapatinib effects on HER3 cell surface expression and mAb3481 internalization were evaluated in human breast (BT474, SKBR3) and gastric (N87) cancer cell lines using flow cytometry. Next, in vivo effects of daily lapatinib treatment on89Zr-mAb3481 BT474 and N87 xenograft tumor uptake were studied. PET-scans (BT474 only) were made after daily lapatinib treatment for 9 days, starting 3 days prior to 89Zr-mAb3481 administration. Subsequently, ex vivo 89Zr-mAb3481 organ distribution analysis was performed and HER3 tumor levels were measured with Western blot and immunohistochemistry. In vitro, lapatinib increased membranous HER3 in BT474, SKBR3 and N87 cells, and consequently mAb3481 internalization 1.7-fold (BT474), 1.4-fold (SKBR3) and 1.4-fold (N87). 89Zr-mAb3481 BT474 tumor uptake was remarkably high at SUVmean 5.6±0.6 (51.8±7.7%ID/g) using a 10 μg 89Zr-mAb3481 protein dose in vehicle-treated mice. However, compared to vehicle, lapatinib did not affect 89Zr-mAb3481 ex vivo uptake in BT474 and N87 tumors, while HER3 tumor expression remained unchanged. In conclusion, lapatinib increased in vitro HER3 tumor cell expression, but not when these cells were xenografted. 89Zr-mAb3481 PET accurately reflected HER3 tumor status. 89Zr-mAb3481 PET showed high, HER3-specific tumor uptake, and such an approach might sensitively assess HER3 tumor heterogeneity and treatment response in patients.

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Section: Discussionmentioning

confidence: 99%

⁸⁹Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

Pool

Kol

Jong

et al. 2017

mAbs

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“…Defining patient subgroups, being person-based rather than variable-based, can help target treatments towards those people who are most likely to benefit [5]. Treatments of some tumours are already stratified according to molecular profiles [16], and research is underway to stratify RA therapies on the basis of inflammatory mechanisms [17, 18]. Identifying patient subgroups in which outcomes are determined by factors other than inflammation might improve allocation of both immunomodulatory therapies and adjunctive pain management strategies [5].…”

Section: Introductionmentioning

confidence: 99%

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data

et al. 2016

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BackgroundRheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs.MethodsData were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined.ResultsFive, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline.ConclusionsDiscordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and activity. These findings could be used to identify a sizeable subgroup of people with RA who might gain added benefit from pain management strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1186-8) contains supplementary material, which is available to authorized users.

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“…Especially, TNXB and ERBB2 are not identified for any cancer by BLP. Actually, ERBB2 is a well-known cancer gene, and it plays a crucial role for certain subtypes of BRCA and OV patients [43], [44]. Third, it is important to note that the individual cancer type approach can only discover a small part of the common gene set for each cancer type ( Fig.…”

Section: Common Mutated Driver Gene Sets Among Two or Multiple Cancermentioning

confidence: 99%

Discovery of cancer common and specific driver gene sets

Zhang

2017

Nucleic Acids Research

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Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found.

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A Review of HER2-Targeted Therapy in Breast and Ovarian Cancer: Lessons from Antiquity – CLEOPATRA and PENELOPE

Cited by 20 publications

References 72 publications

⁸⁹Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

⁸⁹Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data

Discovery of cancer common and specific driver gene sets

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A Review of HER2-Targeted Therapy in Breast and Ovarian Cancer: Lessons from Antiquity – CLEOPATRA and PENELOPE

Cited by 20 publications

References 72 publications

89Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

89Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data

Discovery of cancer common and specific driver gene sets

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Product

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About

⁸⁹Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

⁸⁹Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment