Over the past three decenniums, the perception to treat cancer malignancies has improved from the time when the scientist and researches discovered the idea of inhibitors. The inhibitors are the novel class of chemotherapy which helps to block the activity of gene or protein by consequently binding to it. Since then, many therapies such as targeted antibody regimen, innovative chemotherapy drugs, oncolytic virus therapy, cancer vaccines, stem cell transplant, in addition to surgery has entered the commercial market with the primary motive is to provide treatment for endless patients suffering from cancer. Nevertheless, with the advancement together with evolution in the immunotherapy has led to the development of various inhibitors in the sector of oncology therapy. One such inhibitor is CDC 7 kinase inhibitor used to manage several types of solid cancer such as colon cancer, ovarian cancer, prostate cancer, as well as pancreas cancer in addition to blood cancer like leukemias.
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With the arrival of CDC 7 kinase inhibitor as an innovative treatment regimen has somewhat aided to reduce the cancer burden of multiple patients across the world. Preliminary data from the clinical and laboratories studies have illustrated the over expression of CDC 7 kinase protein results in the formation to tumor cell. One of the foremost causes for development of cancer is the mutation in CDC gene that encodes protein, CDC 7 involved in the process of DNA replication. As an outcome, mutation in CDC 7 encoding gene led to the formation of over expression of CDC 7 protein in conjugation with its protein regulator Dbf4.
The year 2009 was a blessing for the domain of CDC 7 kinase inhibitor owing to the introduction of first CDC 7 kinase inhibitor, BMS-863233/ XL 413 for the treatment of patients suffering from advanced solid cancers, metastatic cancer along with refractory hematologic cancer. The initial studies was sponsored and collaborated by Bristol Myers Squibb in addition to Exelixis.
However, the clinical trial was terminated at the phase I stage in the year 2011 on the account of multiple reasons such as the presence of a accumulated metabolite, buildup of the parent drug at very high levels owing to patients populace that had a poor metabolizer (PM) phenotype in addition to identification of CYP1A2 enzyme that is involved in the metabolism of the parent compound and lack of clinical efficacy. As a consequence, the candidate couldn’t proceed to phase II clinical phase stage. Nonetheless, lately in the year 2023, the contender, BMS- 863233 is also being used with chemotherapy which has correspondingly demonstrated positive outcome by significantly inhibiting cancer cell growth.
Apart from utilizing the CDC 7 kinase inhibitor therapy to cure cancer malignancies, several additional studies are ongoing in the recent year which demonstrates the role of CDC 7 kinase protein in inducing viral replication, consequently leading to the development of viral infection by phosphorylating VP3 protein of the Avibirnavirus, which belongs to the family of Birnaviridae. For that reason, the CDC 7 kinase protein can be employed against cancer majorly solid malignancies as well as viral infection indications.
The domain of CDC 7 kinase inhibitor is growing at a slow; but steady gait. Due to the presence of pharmaceutical companies such as Bristol-Myers Squibb, Exelixis, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nerviano Medical Sciences, Takeda (Millennium Pharmaceuticals, Inc.) and Lin BioScience, Inc in addition to various centers and universities which include University Of Miami, Massachusetts General Hospital, Dana-Farber Cancer Institute, Tianjin Medical University Cancer Institution & Hospital are conducting clinical research in the domain with the primary purpose to developed an advance and innovative inhibitor that will target CDC 7 kinase protein in order to provide treatment for ovarian cancer, prostate cancer, solid tumor, Refractory Hematologic Cancer, Metastatic Cancer, Colorectal Cancer etc.
Hitherto, only a smattering of preclinical and clinical trials is ongoing in the domain. Candidates such as LY3143921 hydrate and SGR-2921 are presently in the phase I clinical trial for the purpose to provide treatment for several cancer indications such as advanced/metastatic solid tumors, refractory hematologic cancer, colorectal cancer, high grade serous ovarian cancer in addition to non-small cell lung cancer (squamous cell variant). Apart from that, recently in the year 2023, contenders such as TQB3824 tablets, LBS-007 in conjugation with TAK-931 are the novel candidates that have been added into the global clinical pipeline for CDC 7 inhibitors. TAK-931 is the solitary medication that has reached the phase II clinical stage to treat advanced non hematologic neoplasms and at present the clinical investigations and studies are ongoing in Japan. All these example aforementioned above propose that the domain of CDC 7 inhibitor is growing and shortly will expand further owing to the increasing cancer and viral diseases indications and rise in the technological advancement.
