Monk's research is primarily focused on the prevention and treatment of gynecologic cancers. He was the pioneer to report the activity of anti-vascular growth factor (VEGF) therapy in ovarian cancer [5] and his papers in the New England Journal of Medicine led to the global approval of antiVEGF therapy in recurrent cervical cancer in 2014 and advanced ovarian in 2018. He was also the lead author on the trial of trabectedin in recurrent ovarian cancer. [6]
Cervical cancer
In his study regarding cervical cancer,Monk reviewed several patients which had uterine sarcoma with cervical involvement,a poor response to preoperative radiation,and a poor response to preoperative radiation. Results of his study indicated that radical hysterectomy after radiation is morbid but might be effective in context of treating patients with small recurrent cervical tumors,cervical cancer that responds poorly to radiation,large cervical tumors,patients unable to undergo brachytherapy for cervical cancer,and uterine sarcomas involving the cervix. [7]
Monk also focused his study on the treatment and prevention of cervical cancer and other HPV-associated malignancies using HPV vaccines,and discussed promises and challenges regarding it. [8] In his paper published in 2007,he demonstrated a methodology for examining the impact of HCII testing in terms of the direct cost of cervical cancer cytological screening. [9]
Monk has been the global leader in systemic therapy in cervical cancer. First in 1999,he contributed to the integration of chemotherapy in treating locally advanced disease with radiation. [10] Then,in 2009 Monk defined the systemic therapy standard of care of recurrent cervical cancer being the combination of a platinum medication and paclitaxel (taxane). [11]
He also investigated the usage of targeted therapies in cervical cancer,and evaluated the antiangiogenesis and endothelial growth factor receptor-related treatments. [12] This led to the global approval of the first targeted therapy in gynecologic cancer. The publication in the New England Journal of Medicine (NEJM) of GOG 240 created a new life prolonging standard treatment for persistent,metastatic and recurrent cervical cancer adding bevacizumab to existing options. [13]
In addition to chemotherapy added to radiation,chemotherapy to treat recurrent cervical cancer and the development of bevacizumab,Monk is also a world leader in advancing immune therapy in cervical cancer. He is the steering committee chair and co-first author for EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9. [14] This phase 3 randomized trial compared cemiplimab vs investigator's choice chemotherapy in recurrent/metastatic cervical carcinoma showed a statistically meaningful and clinically relevant improvement in survival. This is the first randomized trial of immune therapy in cervical cancer to meet its primary and secondary endpoints.
In 2020,he together with co-authors,designed the CALLA trial for the purpose of determining the efficacy of the programmed cell death-ligand 1 blocking antibody,durvalumab,with and following concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in women with locally advanced cervical cancer. [15]
Finally,he also conducted a study regarding the usage of sequential chemotherapy in terms of treating early-stage,post–radical hysterectomy cervical cancer. [16] Most recently,Monk has helped develop antibody drug conjugates such as tisotumab vedotin. This new call of agents has great potential to revolutionize the therapeutic landscape. [17]
Ovarian cancer
Monk published a paper in 2005 focused the role of pegylated liposomal doxorubicin in context of ovarian cancer. Results of his study showed the effectiveness of pegylated liposomal doxorubicin in relapsed ovarian cancer and the improved cardiac safety of pegylated liposomal doxorubicin in comparison to conventional anthracyclines. [18] He also conducted a study based on the contributions of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. [19]
The next major accomplishment for Monk in ovarian cancer came in 2010 with the development of trabectedin in recurrent cancer. This novel medication is approved and used extensively around the world. [20] Monk suggested the integration of the tumor genomic profiling with immune profiling in terms of providing a more comprehensive understanding of an individual patient's tumor leading to improved treatment selection and sequencing. [21]
Monk has also been a leader in the field of inhibition of Poly (ADP-ribose) polymerase (PARP) in advanced and recurrent ovarian cancer. His pivotal publications in the NEJM have led to global approvals and adoption of Niraparib in recurrent and newly diagnosed advanced ovarian cancer. [22]
Monk was the first in the world to describe the activity of bevacizumab in 2005 to treat recurrent ovarian cancer. [23] He and his colleagues then published many more papers on new targets and the inhibition of antiangiogenesis [24] in ovarian cancer culminating in two NEJM medications and global regulatory approval and adoption. [25] [26]
Monk has also focused on rare variants of ovarian cancer such as low-grade serous cancers. His pivotal study of binimetinib showed activity of this MEK inhibitor in a setting of high unmet need. [27] Like ovarian cancer,he is developing immune therapy in ovarian cancer and studies avelumab and nivolumab alone or in combination.
While discussing COVID-19 and ovarian cancer together,Monk explored different alternatives to intravenous (IV) therapies and stated that minimizing patient visits to hospitals and cancer clinics may help mitigate the spread of SARS-CoV-2. [28] Furthermore,he studied the history evidence based on the asbestos and its association with ovarian cancer,while giving reference to WHO's International Agency for Research on Cancer. [29] He also highlighted the application of novel strategies and emerging targets in context of treating the patients with advanced disease. [24]
