ORCID Profile
0000-0002-0150-7765
Current Organisation
National Cancer Institute
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Publisher: Innovative Healthcare Institute
Date: 18-05-2020
DOI: 10.36401/JIPO-20-5
Abstract: PIK3CA mutations resulting in disinhibition of the phosphoinositide 3-kinase (PI3K) pathway are present in approximately a third of estrogen receptor (ER)-positive breast cancer. Recent clinical trials of PI3K inhibition in PIK3CA-mutated metastatic breast cancer have shown improvement in progression-free survival of up to 11 months. We report a 68-year-old woman with metastatic ER-positive breast cancer with PIK3CA mutation who despite having disease progression after four lines of endocrine therapy (ET) attained a complete response (CR) after subsequent addition of a PI3K inhibitor. Remarkably, her CR is still maintained at 5 years. We believe this may be due to the co-occurrence of an NF1 mutation, which increases sensitivity to PI3K inhibition. Our case demonstrates restoration of sensitivity to ET by additional inhibition of PI3K, which resulted in exceptional disease response, far exceeding the expected duration. Hence, we believe that PI3K inhibition in addition to ET should be considered in patients with simultaneous PIK3CA and NF1 mutations.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Chemical Society (ACS)
Date: 03-12-2014
DOI: 10.1021/PH500316U
Publisher: Informa UK Limited
Date: 08-08-2022
DOI: 10.1080/14712598.2022.2108701
Abstract: Despite FDA approval of sipuleucel-T in 2010, endeavors to use immune checkpoint inhibitors in unselected prostate cancer patients have not improved clinical outcomes. These efforts include studies with anti-PD1/PD-L1 and anti-CTLA-4 alone and in combination with existing standards of care. These strategies are generally T-cell centric and disregard the broader complex and pleiotropic components of the prostate cancer tumor microenvironment such as natural killer cells, myeloid-derived suppressor cells, and tumor-associated macrophages. We performed an online literature search and undertook a review of existing preclinical and clinical literature for cytokine-based therapy related to prostate cancer, specifically on interleukin (IL)-2, IL-15, IL-12, IL-23, IL-8, and transforming growth factor (TGF)-β. Cytokine-based therapies present an alternative immune strategy to target the pleiotropic prostate cancer tumor microenvironment beyond T-cells. Future immunotherapy strategies in prostate cancer should address these immune cell populations, which may play more important roles in the prostate cancer tumor microenvironment.
Publisher: Elsevier BV
Date: 08-2015
Publisher: Research Square Platform LLC
Date: 17-05-2023
DOI: 10.21203/RS.3.RS-2924051/V1
Abstract: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase 1 study. We now report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase 1 patients and 7 expansion cohorts. CaboNivo cohorts included: 1) mUC, 2) mRCC, 3) adenocarcinoma of the bladder/urachal, and CaboNivoIpi cohorts included: 1) mUC, 2) mRCC, 3) penile cancer, 4) rare GU tumors, and an exploratory biomarker correlation with peripheral blood immune subsets (NCT02496208). Patients (n = 120) received CaboNivo (n = 64) or CaboNivoIpi (n = 56), with median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59 CaboNivoIpi n = 49), 33 of whom had mUC, ORR was 38% (overall study) and 42% in mUC, complete response 11% and 21%, partial response 27% and 21%, duration of response 20 and 28 months, respectively. Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. In response to treatment, immunosuppressive monocytic MDSCs, classical monocytes, and all dendritic cell subsets decreased Activated proliferative CD4+ T cells and CD8+ T cells and CTLA-4 on CD4+ T cells increased and were associated with improved PFS and OS. Both CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in many metastatic GU histologies, with distinctive patterns of response among innate and adaptive peripheral blood immune subsets and potential differential adaptive resistance in response between CaboNivo and CaboNivoIpi to prolonged effector T-cell activation.
Publisher: Informa UK Limited
Date: 02-05-2023
Publisher: Wiley
Date: 26-10-2020
DOI: 10.1002/CNR2.1310
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2018
DOI: 10.1200/PO.18.00253
Publisher: Informa UK Limited
Date: 27-02-2022
Publisher: Wiley
Date: 07-01-2022
Location: No location found
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Elias Chandran.