Premila Devi Leiphrakpam

The Akt/PKB (protein kinase B) is a major transducer of the phosphoinositide 3-kinase (PI3K) signaling axis, regulating key cellular processes such as growth, proliferation, apoptosis, survival, and migration in both normal and cancer cells. In normal cells, oncoproteins and tumor suppressor proteins within the Akt pathway exist in equilibrium. However, this equilibrium is disrupted in cancer cells due to activating mutations in oncoproteins and inactivating mutations in tumor suppressor proteins. This dysregulation drives tumor growth and progression, making the Akt pathway an attractive target for cancer therapies. A deeper understanding of the molecular mechanisms of the Akt signaling pathway is crucial for developing novel therapeutic agents targeting Akt and its downstream effectors for cancer treatment. This review discusses the role of Akt in cancer, current Akt-targeted agents, their limitations, and future trends.

The global burden of pancreatic cancer has more than doubled in recent decades. It is now the sixth leading cause of cancer-related death worldwide, with an estimated 510,922 new cases and 467,409 deaths in 2022. The incidence of the disease continues to rise annually, with projections indicating a 95.4% increase in new cases by 2050, potentially reaching a total of 998,663 new cases globally. The overall five-year survival rate for pancreatic cancer is 10% worldwide, showing only a modest improvement compared to the past decade. The rising trends in the incidence rates are likely to continue as the global population ages and access to healthcare improves. The relatively low survival rate is primarily attributed to late-stage diagnoses and the lack of an effective screening method. Currently, population-based screening for asymptomatic individuals is not recommended, highlighting the importance of identifying and monitoring individuals at high risk for pancreatic cancer. Numerous studies have highlighted the differences in the molecular pathology of pancreatic cancer, underscoring the need for continued research to better understand these differences. The silent progression of the disease, poor prognosis, lack of screening options, and the necessity to improve our comprehension of its molecular characteristics emphasize the critical need for ongoing monitoring of disease trends at the population level. This review article analyses trends in the incidence of pancreatic cancer and its histological subtypes and provides an update on its molecular subtypes.

The global cancer burden is expected to rise over the next few decades, with an equally significant increase in the need for cancer surgical services. It is well known that gross inequities exist in accessing cancer surgical care on the global stage. The goal of this manuscript is to highlight the inequities in accessing cancer surgical care and outline some strategies to address them. We used GLOBOCAN 2022 to document the current and predicted rise in the future cancer burden for the various income groups, as defined by the World Bank Group. Data from relevant agencies such as the International Atomic Energy Agency (IAEA), World Bank Group, and relevant publications were used to quantify current and future workforce (surgical and relevant other health professions) needs, number of imaging modalities, hospital capacity, and healthcare expenditure per capita. Our study demonstrates that there are extreme variations in cancer burden on the global stage as well as inequities in all domains of cancer surgical care pathways, based on income status. Low-income (LICs) and lower-middle-income countries (LMICs) will experience a proportionally larger increase in cancer burden over the next few decades. At the same time, LICs and LMICs were noted to have severe shortages in all elements of the cancer surgical care pathways ranging from the number of cancer surgeons and other oncology professionals, hospital beds, and imaging modalities, when compared to high-income countries (HICs). Health care expenditure per capita also demonstrated variations with the highest rates noted in the HICs. This study highlights the inequities in access to cancer surgical care on the global stage. To address these challenges, we have proposed some strategies derived from the 2023 Lancet Oncology Commission on Global Cancer Surgery report, which can realistically be accomplished in a timeframe of 5–15 years.

In the last decade, pathway-specific targeted therapy has revolutionized colorectal cancer (CRC) treatment strategies. This type of therapy targets a tumor-vulnerable spot formed primarily due to an alteration in an oncogene and/or a tumor suppressor gene. However, tumor heterogeneity in CRC frequently results in treatment resistance, underscoring the need to understand the molecular mechanisms involved in CRC for the development of novel targeted therapies. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/Akt/mTOR) signaling pathway axis is a major pathway altered in CRC. The aberrant activation of this pathway is associated with CRC initiation, progression, and metastasis and is critical for the development of drug resistance in CRC. Several drugs target PI3K/Akt/mTOR in clinical trials, alone or in combination, for the treatment of CRC. This review aims to provide an overview of the role of the PI3K/Akt/mTOR signaling pathway axis in driving CRC, existing PI3K/Akt/mTOR-targeted agents against CRC, their limitations, and future trends.

Technological advancement and improved training strategies have transformed the healthcare practice environment in the last few decades. Simulation has evolved as one of the leading training models for the next generation of healthcare professionals. Simulation-based training enables healthcare professionals to acquire knowledge and skills in a safe and educationally oriented environment and can be a valuable tool for improving clinical practice and patient outcomes. The field of healthcare simulation has been rapidly growing, and various graduate medical education programs around the world have started incorporating this modality into their curricula. In graduate medical education, simulation-based training helps implement an outcome-based curriculum that tests the trainee's actual skill level as the primary factor for the trainee's competency rather than relying on the current model of a predetermined training period. However, the major challenge revolves around developing an educational curriculum incorporating a simulation-based educational model, understanding the value of this new technology, the overall cost factor, and the lack of adequate infrastructure. Hence, embracing the full potential of simulation technology in graduate medical education curricula requires an innovative approach with participation from institutions and stakeholders.

Tumor profiling and targeted therapy revolutionized the treatment strategies of metastatic colorectal cancer (mCRC) in the last decade. The heterogeneity of CRC tumors plays a critical role in the development of treatment resistance, which underscores the need to understand the molecular mechanism involved in CRC to develop novel targeted therapeutic strategies. This review provides an overview of the signaling pathways driving CRC, the existing targeted agents, their limitations, and future trends.

In the next two decades, the global cancer burden is expected to rise by 47%, and the demand for global cancer surgery will increase by 52%. At present, only 25% of the estimated 80% of patients needing surgical intervention have access to timely surgical care. The shortage of a trained workforce of surgical oncologists is one of the main barriers to providing the optimal surgical intervention needed for cancer patients. Some of the contributing factors to the shortage of trained surgical oncologists are variations in the current global educational platforms, long training programs, and physician burnout. Therefore, the availability of a credible training framework and a sustainable certification pipeline for future surgical oncologists is critical to meet the global demand for an adequate healthcare workforce. The current surgical oncology educational program is a time-based construct that trains surgeons to function seamlessly in the multidisciplinary care of cancer patients. However, there is a lack of flexibility in the training framework and timeline despite differences in trainees’ abilities. Developing a globally acceptable standard curriculum for surgical oncology training based on the competency-based medical education (CBME) framework and tailoring it to local needs can increase the surgical oncology workforce ready to tackle the rising cancer burden. However, successful implementation of the global CBME-based surgical oncology training curriculum requires an innovative approach to ensure that this framework produces a competent surgical oncologist that meets the local needs.

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology. Objective: To develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI. Methods: Rats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO₂), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals. Results: The current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO₂ and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals. Conclusion: We have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

Background: Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. Methods: Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO₂), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. Results: Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO₂ by approximately 31%, PaO₂/FiO₂ ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. Conclusions: This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.