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1.
Clin Med Insights Oncol ; 18: 11795549241260534, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911453

RESUMO

Antibody-drug conjugates (ADCs), combining the cytotoxicity of the drug payload with the specificity of monoclonal antibodies, are one of the rapidly evolving classes of anti-cancer agents. These agents have been successfully incorporated into the treatment paradigm of many malignancies, including non-small cell lung cancer (NSCLC). The NSCLC is the most prevalent subtype of lung cancer, having a considerable burden on the cancer-related mortality and morbidity rates globally. Several ADC molecules are currently approved by the Food and Drug Administration (FDA) to be used in patients with NSCLC. However, the successful management of NSCLC patients using these agents was met with several challenges, including the development of resistance and toxicities. These shortcomings resulted in the exploration of novel therapeutic targets that can be targeted by the ADCs. This review aims to explore the recently identified ADC targets along with their oncologic mechanisms. The ADC molecules targeting these biomarkers are further discussed along with the evidence from clinical trials.

2.
Med Oncol ; 40(1): 48, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36520261

RESUMO

Triple negative breast cancer (TNBC) portraying deficient expression of estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) is known to be the most aggressive subtype associated with poor prognosis and interventional strategies limited to chemotherapy and breast conserving surgery. Some TNBC incidences have also been reported with positive circ-HER2 expression thus rendering circ-HER2 a potential immunotherapy target to direct drug development. Resistance and recurrence reported with traditional approaches has led us towards the application of immunotherapeutic interventions owing to their anti-tumor efficacy. This review provides an elaborative insight on potential molecular biomarkers to be targeted by immunotherapy. Additionally, clinical trials proposing the application of immunotherapy in neoadjuvant, adjuvant and metastatic TNBC setting have also been included. The gathered evidence indicates a positive application of immunotherapy in TNBC with therapeutic limitation available only owing to the possibility of adverse events which can be dealt considering risk-to-benefit ratio. Furthermore, potential targets to aim for therapeutic vaccines along with evidence from clinical trials have also been mentioned.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Imunoterapia , Receptores de Estrogênio/metabolismo , Terapia Neoadjuvante
3.
Med Oncol ; 40(1): 25, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36456774

RESUMO

Triple-negative breast cancer (TNBC) showcases a labyrinthine network exhibiting deficient expression of Estrogen receptor (ER), Progesterone receptor (PR), and Human-epidermal growth factor receptor-2 (HER2). This restricts the conventional chemotherapeutic, hormonal, and few targeted regimens in showing efficient anti-tumor response. Antibody-drug conjugates (ADCs) are target-specific conjugates comprising a monoclonal antibody attached to the desired cytotoxic payload with the support of a stable linker. They are designated as one of the encouraging sets of targeted therapies that have unveiled affirmative outcomes owing to increased specificity in targeting the undetectable or deficiently expressed targets. Another virtue of ADCs lending superiority to this approach is the presence of inherent bystander effect which has a detrimental influence on the tumor microenvironment (TME) devoid of antigen expression. In the current scenario, FDA-approved Sacituzumab govitecan is widely being utilized to mitigate TNBC while many other ADCs are being studied in clinical trials. Additionally, a focus has been set on revelation of application of Trastuzumab deruxtecan in HER2-low metastatic breast cancer which widens the current therapeutic horizon dealing with such carcinomas. After making an effort towards sketching ADCs profile, we conclude that this novel approach deserves to be investigated through future campaigns owing to its remarkable bystander effect, ability to precisely recognize the antigen and spare the naïve cells from detrimental toxicity. Exploration of the remarkable potential of Sacituzumab govitecan in multiple indications including TNBC portrays the prominence of ADCs and prompts the bright future of this therapeutic approach. In this review, we present the basic foundation of ADCs alongside summarizing the building blocks of several ADCs used in TNBC. Furthermore, by shedding light on the therapeutic regimens and concomitant effects of various ADCs derived from the supportive backbone of clinical trials, we have attempted to convene several segments of ADCs and portray their potentialities time ahead.


Assuntos
Carcinoma , Imunoconjugados , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Imunoconjugados/uso terapêutico , Receptores de Estrogênio , Efeito Espectador , Microambiente Tumoral
4.
Cancers (Basel) ; 15(1)2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36612226

RESUMO

Triple-negative tumors are progressively delineating their existence over the extended spectrum of breast cancers, marked by intricate molecular heterogeneity, a low overall survival rate, and an unexplored therapeutic approach. Although the basal subtype transcends the group and contributes approximately 80% to triple-negative breast cancer (TNBC) cases, the exceptionally appearing mesenchymal and luminal androgen receptor (LAR) subtypes portray an unfathomable clinical course. LAR with a distinct generic profile frequently metastasizes to regional lymph nodes and bones. This subtype is minimally affected by chemotherapy and shows the lowest pathologic complete response. The androgen receptor is the only sex steroid receptor that plays a cardinal role in the progression of breast cancers and is typically overexpressed in LAR. The partial AR antagonist bicalutamide and the next-generation AR inhibitor enzalutamide are being assessed in standard protocols for the mitigation of TNBC. There arises an inevitable need to probe into the strategies that could neutralize these androgen receptors and alleviate the trajectory of concerning cancer. This paper thus focuses on reviewing literature that provides insights into the anti-androgenic elements against LAR typical TNBC that could pave the way for clinical advancements in this dynamic sphere of oncology.

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