Chemotherapy For Oral Cancer Research Articles

Nonadherence to oral cancer chemotherapy in hepatocellular carcinoma: prevalence and predictive factors in Vietnam

PurposeStandard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC.Patients and methodsIn 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires.Results54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32–3.98, P = 0.003; OR = 4.36, 95% CI = 0.95–19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08–3.55, P = 0.024; OR = 1.86, 95% CI = 1.1–3.14, P = 0.02; OR = 2.34, 95% CI = 1.29–4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001).ConclusionsThis study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence.

3D stem-like spheroids-on-a-chip for personalized combinatorial drug testing in oral cancer

BackgroundFunctional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, lack of clinical correlation, and mono-drug therapy testing. Furthermore, personalized microfluidic models based on spheroids derived from oral cancer patients remain to be thoroughly validated. Overcoming the limitations, we develop 3D printed mold-based, dynamic, and personalized oral stem-like spheroids-on-a-chip, featuring unique serpentine loops and flat-bottom microwells arrangement.ResultsThis unique arrangement enables the screening of seven combinations of three drugs on chemoresistive cancer stem-like cells. Oral cancer patients-derived stem-like spheroids (CD 44+) remains highly viable (> 90%) for 5 days. Treatment with a well-known oral cancer chemotherapy regimen (paclitaxel, 5 fluorouracil, and cisplatin) at clinically relevant dosages results in heterogeneous drug responses in spheroids. These spheroids are derived from three oral cancer patients, each diagnosed with either well-differentiated or moderately-differentiated squamous cell carcinoma. Oral spheroids exhibit dissimilar morphology, size, and oral tumor-relevant oxygen levels (< 5% O2). These features correlate with the drug responses and clinical diagnosis from each patient’s histopathological report.ConclusionsOverall, we demonstrate the influence of tumor differentiation status on treatment responses, which has been rarely carried out in the previous reports. To the best of our knowledge, this is the first report demonstrating extensive work on development of microfluidic based oral cancer spheroid model for personalized combinatorial drug screening. Furthermore, the obtained clinical correlation of drug screening data represents a significant advancement over previously reported personalized spheroid-based microfluidic devices. Finally, the maintenance of patient-derived spheroids with high viability under oral cancer relevant oxygen levels of less than 5% O2 is a more realistic representation of solid tumor microenvironment in our developed device.Graphical

Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Implications of Chemotherapy, Radiation therapy, and Surgical treatment in Oral Cancer

Oral cancer includes both the cancers of the mouth and back of the throat. This literature review investigates viable treatment modalities for adult patients diagnosed with oral cancer including the comparison of chemo/radiation therapy, surgery, and new treatment modalities. Surgical interventions are often the initial treatment, depending on tumor characteristics, and may require reconstructive procedures. Chemotherapy and radiation therapy, while effective, present challenges such as side effects such as nausea, vomiting, hair loss, and fatigue. With surgery, there is the consideration of different types of therapies. Post-operative care, lifestyle implications, and treatment success vary among these modalities. New treatments such as gene therapy and immunotherapy are also starting to appear. Findings suggest the drawbacks and the advantages of different treatments and possible preventive measures.

Neoadjuvant chemotherapy for advanced oral cavity cancer.

Neoadjuvant chemotherapy for advanced oral cavity cancer.

Metronomic Chemotherapy in Oral Cancer: A Review.

Treatment of locally advanced oral cancer requires multidisciplinary care, including surgery, radiotherapy, and chemotherapy, which varies based on the stage of the disease, site of involvement, and surgical access. Oral cancer usually presents with an increased recurrence rate and potential for distant metastatic spread. It confers a poor prognosis with a 50% mortality rate after five years. Oral metronomic chemotherapy aims to achieve higher patient compliance due to its ease of administration, lower dosage, and lesser side effects than conventional IV regimens of platinum-based drugs. In this review, we have summarized the relevant literature to benefit the readers regarding the potential application of metronomic therapy in the management of oral cancer.

Guideline-compliant adjuvant chemotherapy for resected high risk oral cavity cancer: Homefield advantage

PurposeFactors that are associated with failure to receive guideline-compliant adjuvant chemotherapy after resection of high-risk oral cavity cancer are understudied. Here, we performed a retrospective cohort study of surgically treated patients with oral cavity squamous cell carcinoma to determine rates of guideline-compliant adjuvant chemotherapy and to examine patient factors associated with receiving guideline-compliant chemotherapy. Study designRetrospective cohort. SettingTwo tertiary care referral centers. MethodsPatients with resected high-risk oral cavity squamous cell carcinoma and known adjuvant therapy details were included. Extranodal extension or positive margins were considered high-risk features for which adjuvant chemoradiation was indicated. Patient factors were examined to determine associations with receiving on-guidelines treatment. Univariable and multivariable logistic regression were used to determine significance of associations. Results75 patients were included. 36 (48 %) patients received guideline-compliant cisplatin. In total, 39 (52 %) patients did not receive guideline-compliant chemotherapy. On multivariable analysis, meeting with a university medical oncologist was significantly associated with the receipt of guideline-compliant cisplatin (OR 6.38, 95 % CI 2.26–20.0, p < 0.001). ConclusionAdherence to on-guidelines treatment can be difficult to achieve in patients with advanced stage head and neck cancer. Meeting with university medical oncology is associated with an increased chance of receiving guideline-compliant chemotherapy.

Low-dose immunotherapy as a potentiator to increase the response with neo-adjuvant chemotherapy in oral cancers.

Neo-adjuvant chemotherapy (NACT) is utilized in locally advanced oral cancers to reduce the tumor burden and downstage the tumor to be amenable for definitive surgical management. Its long-term results compared to upfront surgical resection was not encouraging. Immunotherapy has now been used not only in recurrence and metastatic setting but also in the locally advanced tumor management regimens. The purpose of this concept paper is to bring forward the rationale to use a fixed low-dose immunotherapy agent as a potentiator to the standard NACT regimen and recommend their future investigation in oral cancer management.

Abstract 3314: Circulatory altruistic stem cells as a prognostic biomarker for platinum based chemotherapy in oral cancer

Abstract Background: Head &amp; neck cancer is the 4th common cancer, and most of them are diagnosed late, andtreated with cisplatin monotherapy. In these subsets of patients, immunotherapy has been tried, butwithout major success [1]. We speculate that circulating altruistic mesenchymal stem cells may serve asbiomarker for immunosuppression. Previously, we showed that oral cancer CSCs reprogram MSCs toaltruistic phenotype [2, 3], an embryonic stem cell like phenotype having niche defending ability [5].Here, we propose to test the immunosuppressive ability of ASCs, and their detection in the circulation ofhead &amp; neck cancer subjects undergoing platinum based chemotherapy. Method: The immunosuppression test: immunosuppressive secretory factors, mixed lymphocytereaction (MLR) assay, and a Boyden chamber based co-culture assay with NK cells [4]. Next, weobtained circulating CD271+/CD45- cells of stage IV head and neck cancer subjects (n=20) (5). Kaplan-Meier survival analysis and log-rank test to find association between the presence of circulatory ASCsand overall survival (OS). Result: CSCs including primary tumor obtained CSCs reprogram CD271+ MSCs to ASC phenotype;these cells secrete high level of Nitric oxide, IDO, TGF-beta, IL-10 and PGE-2. ASCs exhibited markedimmunosuppression in the MLR test. In Boyden chamber assay, ASCs markedly decreased the numberof NKG2D+ NK cells, and CD8+ T cells by 4-5 fold, whereas increased the CD4+/FoxP3/CD25- T-reg cells by 3-fold . Importantly, these 12 out of 20 patients showed poortreatment response to platinum therapy. The OS at 6 months was 24.6% for circulating ASC-positivepatients and 47.4% for circulating ASC- negative patients (log-rank test,). Conclusion: The circulatory ASCs could be a promising biomarkers for immunotherapy.

Abstract A065: Prospective cohort study of a pharmacist-driven medication management program to improve oral cancer therapy adherence in an underserved, diverse urban setting

Abstract Introduction: Patient adherence is critical to the efficacy of oral cancer chemotherapy. At a major safety net hospital, we sought to define the adherence to oral cancer therapy amongst our diverse and socioeconomically disadvantaged patient population. We designed a high-touch, pharmacist driven program called Boston Medical Center’s Specialty Pharmacy Adherence Program (B-SPAP), to see if this intervention could improve adherence to oral cancer treatment. Methods: We conducted a prospective intervention study of adult patients undergoing treatment with an oral oncology agent for advanced cancer or hematologic malignancy. The intervention incorporated the Multinational Association of Supportive Care in Cancer Oral Agent Teaching Tool by a clinical pharmacist for 30-60 minutes at initial, 3, 6, and 12 month study visits. Patients completed Patient Activation Measure (PAM) and Trust in Physician (TIP) surveys during visits. The primary endpoints were adherence (medication adherence ratio (MAR) (= sum of days’ supply for all fills in period/number of days in period) x100), and persistence (presence or absence of a &amp;gt;/= 45 day treatment gap). We utilized a 2:1 matched historical control design on type of chemotherapy agent. Linear regression models examined differences in adherence and persistence between intervention and controls. Data: There were 218 patients, 74 intervention and 144 historical controls. 54% of patients identified as Black, 28% Caucasian, 7% Asian, 6% other, 17% as Hispanic/Latino. 37% do not use English as their preferred language. 24% reported finishing high school. 30% are on Medicaid, 42% on Medicare, 10% had commercial insurance. The MAR in the intervention group was 92 (SD 14.6) compared with 93 (SD 10.8) in the historical control group (p=0.4). 78% of patients in the intervention group were persistent compared with 80% of historical controls (p=0.9). Non-English speaking patients had higher MAR=94.5 than English speaking patients, MAR=91 (β 3.5, SE 1.7, p=0.04). There were no differences in MAR in relation to age, marital status, or charlson comorbidity index. For the intervention patients, the average TIP Score was 48 (max of 55). TIP score did not differ by race (white=47, non-white 49, p=0.4) or language (English=49, non-English=47, p=0.3). The average PAM score was 43 (max of 52). Conclusions: Adherence to oral cancer therapies amongst our diverse patient population is high, over 90 adherent days in a 100 day period. Our high-touch, pharmacist driven intervention did not improve adherence or persistence between controls and intervention due to high rates in the control population. Interestingly we found that non-English speaking patients were more likely to be adherent than English speaking patients. Our findings suggest that equal access among a diverse patient population at a safety net institution can result in high adherence and positive outcomes despite socio-demographic factors that often lead to disparities in cancer care. Citation Format: Claire E.P. Smith, David Hughes, Scott Gould, Anne Buck, Naomi Y. Ko. Prospective cohort study of a pharmacist-driven medication management program to improve oral cancer therapy adherence in an underserved, diverse urban setting [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A065.

Successful surgical extraction of an impacted mandibular third molar in a patient treated with head &amp; neck radiotherapy and chemotherapy for oral cancer

Osteoradionecrosis (ORN), a pathological condition characterized by a nonvital bone occurring in the site of radiation injury, is one of the significant risks following extraction of highly impacted third molar teeth in patients treated with head &amp; neck radiotherapy for oral cancer. Therefore, the surgery’s meticulous planning is essential to avoid such complications. This case report describes a 63-year-old male patient diagnosed with an impacted lower third molar (tooth #38) with concurrent basal cell carcinoma of the right ear and squamous cell carcinoma of the right vocal cord treated with radiotherapy. Taking into account the patient’s health status, a minimally invasive osteotomy and a corono-radicular separation procedure were performed. This procedure allowed us to reduce the risk of mandibular ORN. Three years later, the healing was complete, and the situation was stable.

The role of lncRNAs and XIST in oral cancer.

Long non-coding RNA (lncRNA) plays a significant role in the pathogenesis of many human malignant tumors, including oral cancer. LncRNA can act as a gene regulator in a variety of cancers. It regulates the growth of malignant cells via many cellular signal pathways such as the PI3K (phosphoinositide 3-kinase)/AKT (α-serine/threonine-protein kinase) pathway. In this review, we have analyzed the role of lncRNAs, such as lncRNA X inactive specific transcript (XIST), in oral cancer, including its effects on the proliferation, apoptosis, invasion, migration, and resistance to chemotherapy of oral cancer. We have also focused on the role of lncRNA XIST as the core of X chromosome inactivation. Here, we provide a brief overview of the role of many kinds of lncRNAs, including XIST, which provides a theoretical basis for the study of the role of XIST in oral cancer. Our review may provide a new direction for the study of the occurrence, development, and prognosis of oral cancer and provide a new target for its treatment.

A case of pulmonary thromboembolism occurring during chemotherapy for oral cancer

A case of pulmonary thromboembolism occurring during chemotherapy for oral cancer

Anticancer activity of heptazoline against the SCC-15 human oral cancer cells and inhibition of PI3K/AKT signalling pathway

Current research endeavours are focusing to develop potent chemotherapy for oral cancer. Consistently, this study examined the anticancer effects of heptazoline on the human oral cancer cells. The findings of the present study revealed that heptazoline suppressed the growth of all the oral cancer SCC-15 oral cancer cells (IC50; 12 µM) with very low cytotoxic effects on the normal hTRET-OME cells (IC50; 85 µM). The comet and DAPI assay showed DNA damage as well other signs of apoptosis induced by heptazoline in SCC-15 cells. Annexin V/PI assay revealed that apoptotic SCC-15 cells increased from 3.5% at 0 µM to 21.27% at 24 µM of heptazoline Additionally, the expression of Bax was upregulated and that of Bcl-2 was downregulated upon heptazoline treatment of the SCC-15 cells. Heptazoline also increased the expression of caspase-3 further confirming the induction of apoptosis. Investigation of the effects of heptazoline on the PI3K/AKT signalling showed a remarkable decrease in the phosphorylation of PI3K and AKT. Taken together, the findings of the study suggest that heptazoline has potent anticancer activity and may serve as a lead molecule in oral cancer treatment.

Antiproliferative activity of an angular furanocoumarin-oroselol in human oral cancer cells is mediated via autophagy induction, inhibition of cell migration, invasion, and downregulation of PI3K/AKT signalling pathway.

Oral carcinoma is a lethal type of cancer associated with huge morbidity and mortality. Oral cancer patients show a very low survival chances even if diagnosed at early stages. The need for novel naturally occurring chemotherapeutic drugs increases due to high cost and toxicity of currently used clinical drugs. Present study was designed to investigate anticancer property of oroselol, keeping in view the medicinal potential showed by coumarin subclass furanocoumarins. MTT assay and clonogenic assays were implemented for viability assessments. Transmission electron microscopy was used for autophagic studies. The transwell chambers assay was used to investigate the migration and invasion. Western blotting was performed to determine the expressions levels of autophagy and PI3K/AKT signalling related proteins. Results showed that oroselol could potentially inhibit viability of oral cancer SSC-4 cells in time- and dose-reliant fashion. The antiproliferative effects were mediated through autophagy induction as indicated by formation of autophagosomes and enhanced LC3-l expressions and reduced LC3-II and p62 expressions. Cancer cell migration and invasion was potentially supressed by oroselol cell treatment. The PI3K/AKT signalling pathway was blocked potentially by oroselol in SSC-4 cells which showed reduced phosphorylation of PI3K and AKT. In conclusion, oroselol holds a significant potential to induce autophagy-related antiproliferative effects along with inhibition of cell migration, cell invasion, and PI3K/AKT signalling pathway. Therefore, oroselol may prove to be a lead molecule in oral cancer chemotherapy provided further in vivo and toxicological studies are performed on it.

GSDME Is Related to Prognosis and Response to Chemotherapy in Oral Cancer

Gasdermin E (GSDME), as the major executive protein of pyroptosis, has been considered to be linked to antitumor immunity in recent years. However, the role of GSDME in oral squamous cell carcinoma (OSCC) remains to be elucidated. Here, by using a human OSCC tissue microarray, human OSCC tissue, and Tgfbr1/Pten conditional knockout mice, we found that GSDME was strongly expressed in OSCC and that GSDME expression in primary tumors was higher than that in metastatic lymph nodes. In addition, GSDME expression in OSCC was positively related to better prognosis. Moreover, GSDME-mediated pyroptosis occurred upon stimulation with chemotherapy drugs, and functional knockdown of GSDME attenuated the cisplatin-induced antitumor effect. Consistent with these results, bioinformatic analysis indicated that GSDME expression was positively correlated with the sensitivity of a number of antitumor drugs approved by the US Food and Drug Administration. Inhibition of GSDME expression by small interfering RNA in SCC7 cells significantly increased the expression of the cancer stem cell markers, CD44 and ALDH1. Furthermore, multiplexed immunohistochemistry and flow cytometry indicated that the expression of GSDME positively correlated with tumor-infiltrating CD8+ T cells, granzyme B, and M1 phenotype macrophages. Collectively, these findings demonstrated that GSDME is a potential positive prognostic factor of OSCC, and GSDME-mediated pyroptosis induced by chemotherapy plays a role in antitumor response.

Bacterial Antigens Reduced the Inhibition Effect of Capsaicin on Cal 27 Oral Cancer Cell Proliferation.

Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells’ suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.

Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition.

The increasing incidence of resistance to chemotherapeutic agents has become a major issue in the treatment of oral cancer (OC). Epithelial-mesenchymal transition (EMT) has attracted a great deal of attention in recent years with regard to its relation to the mechanism of chemotherapy drug resistance. EMT-activating transcription factors (EMT-ATFs), such as Snail, TWIST, and ZEB, can activate several different molecular pathways, e.g., PI3K/AKT, NF-κB, and TGF-β. In contrast, the activated oncological signal pathways provide reciprocal feedback that affects the expression of EMT-ATFs, resulting in a peritumoral extracellular environment conducive to cancer cell survival and evasion of the immune system, leading to resistance to multiple chemotherapeutic agents. We present an overview of evidence-based chemotherapy for OC treatment based on the National Comprehensive Cancer Network (NCCN) Chemotherapy Order Templates. We focus on the molecular pathways involved in drug resistance related to the EMT and highlight the signal pathways and transcription factors that may be important for EMT-regulated drug resistance. Rapid progress in antitumor regimens, together with the application of powerful techniques such as high-throughput screening and microRNA technology, will facilitate the development of therapeutic strategies to augment chemotherapy.

Computational Fluid Dynamics Study of Superselective Intra-arterial Chemotherapy for Oral Cancer: Flow Simulation of Anticancer Agent in the Linguofacial Trunk

Superselective intra-arterial chemotherapy (SSIAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, the agent distribution between the lingual artery and facial artery (FA) is not clear in SSIAC for patients with the linguofacial trunk. The agent distribution in the SSIAC method was investigated using computational fluid dynamics (CFD). Ten three-dimensional vessel models were created from CT images of two patients with oral cancer (patients A and B) with the linguofacial trunk. Catheter models were combined with vessel models to mimic intra-arterial infusion, and the agent flow was analyzed. In patient A models, the agent distribution varied depending on the catheter tip position in the linguofacial trunk, while all anticancer agents flowed into the FA only in patient B models. This study revealed that the behavior of the agent in the common trunk is determined by the blood flow field which depends on the topography of the vessels in each patient. Therefore, the catheter tip position should be changed according to the vessel topography to deliver anticancer agents into the tumor-feeding artery. Moreover, CFD can be a useful method to predict the agent flow for each patient before SSIAC.

Oleanolic acid-conjugated poly (D, l-lactide)-based micelles for effective delivery of doxorubicin and combination chemotherapy in oral cancer

Here, an amphiphilic polymer, oleanolic acid conjugated methoxy-poly (ethylene glycol)-poly (D, l-lactide) (mPEG-PLA-OA) was synthesized, which self-assembled in aqueous environment and loaded the poorly soluble anticancer agent, doxorubicin. Various physico-chemical characterization studies on polymer and DOX-loaded polymeric micelles (DOX-mPEG-PLA-OA) at various drug to polymer (1:5/10/15) (DTP) ratios were performed, which included characterizations via UV, IR, NMR spectroscopy and gel permeation chromatography for polymers, and dynamic light scattering, DSC, XRD techniques, determination of critical micelles concentration, percent drug loading, encapsulation efficiency, drug release, kinetic stability and haemolysis studies for micelles. Further, DOX-mPEG-PLA-OA were evaluated for their cellular uptake, cytotoxicity, ability to induce apoptosis, DNA fragmentation, nuclear damage, ROS generation, and mitochondrial membrane depolarization in oral squamous cell carcinoma (FaDu HTB-43) and murine melanoma (B16F10) in monolayer and in FaDu HTB-43 3D cell culture systems. DOX-mPEG-PLA-OA at DTP ratios. 1:5/10/15 showed physico-chemical parameters in the following range: particle sizes. ~210.3–225.1 nm, DOX encapsulation efficiency. 29–35% and DOX-loading. 2.2–5%. DOX-mPEG-PLA-OA micelles (1:15) were stable as proven by kinetic stability study, and showed sustained release of encapsulated DOX for over 60 h. The cell viability study revealed that DOX-mPEG-PLA-OA micelles (1:15) demonstrated highest time- and dose dependent cytotoxicity compared to free DOX and micelles of other DTP ratios. Following treatment, the DOX-mPEG-PLA-OA micelles (1:5/10/15) induced highest cellular apoptosis in the range of 28.17–48.1, compared to free DOX (9.5 ± 2.52), and mPEG-PLA-OA micelles (25.4 ± 2.91), DOX-mPEG-PLA-OA micelles (1:15) being the strongest apoptosis inducer (48.1 ± 2.68) as determined by flow cytometry-mediated annexin V assay. DOX-mPEG-PLA-OA micelles (1:15) induced significantly higher DNA fragmentation, nuclear condensation, ROS generation, and mitochondrial membrane permeabilization compared to free Dox in monolayer FaDu HTB-43. DOX-mPEG-PLA-OA micelles (1:15) showed reasonably higher penetration and stronger growth inhibition in FaDu HTB-43 spheroids compared to free DOX and micelles of other DTP ratios. In-vivo pharmacokinetic studies showed that the DOX-mPEG-PLA-OA micelles demonstrated enhanced blood circulation time with decreased rate of clearance than free Dox (t1/2. 33.5 ± 2.5 h vs. 1.77 ± 0.32 h, and Cmax. 59.7 ± 2.2 vs. 2.3 ± 0.1, respectively). Immunohistochemistry revealed no significant toxicity in major organs of DOX-mPEG-PLA-OA micelles treated rats. The series of studies indicated that the OA-conjugated mPEG-PLA micelles served as an efficient nanocarriers for DOX, demonstrated DOX, and OA combined superior anticancer effect, sustained DOX level in blood circulation for up to 96 h, and no sign of major organs toxicity. Therefore, this newly developed DOX, OA combined micelles displayed its potential as promising alternative to DOX-based conventional therapy, and warrants further investigation for clinical application, especially for the treatment of oral cancer.