ASCO建议：未来癌症研究集中的领域（2020年）

根据ASCO原则提出的未来癌症研究集中的九个领域。目标是希望能够加速抗癌诊疗研发进展，提高生存，提高生存质量。这些优先研究领域已经过多年研究，有可能在不远的未来获得快速发展，或者重要的突破。

ASCO提出的九大研究领域如下：


1. 识别能够预测免疫疗法反应的策略

Identify Strategies That Better Predict Response to Immunotherapies

Cancer immunotherapy encompasses a broad range of medicines and treatment approaches, including vaccines, immune checkpoint inhibitors, and most recently, cellular therapies. These interventions have improved the outlook for multiple cancers, producing long-lasting remissions that  can last for years in some patients. At present, however, long-term disease control occurs in just a minority of pa- tients. In addition, immunotherapies can cause substantial adverse effects that can be life-threatening and, in some cases, permanent. Methods to identify patients most likely to benefit from immunotherapy and those at high risk for severe adverse events are urgently needed. The ability to adequately assess benefits and risks of immunotherapy for each individual will lead to better outcomes for patients.

Priority focus areas:

Identify factors that predict response, long-term dis- ease control, prolonged survival, treatment resistance, and adverse events for all types of immunotherapies

Develop blood- and tissue-based biomarkers and novel immune-response signatures that predict treatment benefit

Develop predictive models and algorithms that assign risk of severe immune-related toxicities based on readily available patient data


针对不同类型的免疫治疗，确定可以预测治疗反应、长期疾病控制、更长生存期、治疗抵抗的因素；发现可以预测治疗效果的血液和组织生物标志物根据现有患者数据，制定针对严重副作用风险的预测模型和算法


2. 明确术后（辅助）治疗的最优受益人群

Better Define the Patient Populations That Benefit From Postoperative (Adjuvant) Therapy

A wide range of therapies are recommended to patients after surgery. These therapies, referred to as adjuvant treatments, aim to reduce the risk of recurrence and cancer-related death. Although such therapy has been associated with dramatic improvements in survival for some patients, studies have shown that the risks can outweigh the benefits for others. It is important to ensure that patients who receive adjuvant therapy are the ones most likely to benefit. Eliminating its use in those who do not benefit will be an important step in optimizing care and eliminating unnecessary adverse effects and costs for patients in whom the benefits are unlikely to outweigh the risks.

Priority focus areas:

Determine factors that identify patients most likely to benefit, or those unlikely to benefit, from adjuvant therapy, including, but not limited to, clinical, patho- logic, genomic, biochemical, immunologic, and envi- ronmental or social factors

Develop analytically and clinically valid biomarker tests with proven clinical utility to identify recurrence risk after treatment of the primary tumor and de- termine the best options for patients with different degrees of risk

确定哪些因素可以发现最有可能从辅助治疗获益或者不太可能获益的患者，这些因素包括但不限于临床、病理、基因组、生化、免疫、环境或社会因素。研发且具有临床有效性且可分析的生物标志物检测，可以来确定原发肿瘤治疗后的复发风险，或者确定不同风险程度患者的最佳治疗方案。


3. 细胞疗法在实体瘤临床应用

Translate Innovations in Cellular Therapies to Solid Tumors

Recent FDA approvals of CAR-T therapies in leukemia and lymphoma are true milestones in cancer therapy, as sig- nified by ASCO’s 2018 Advance of the Year designation. Although cellular therapies that use a patient’s modified cells to harness the immune system are transforming care for some patients with blood-based cancers, there are limited data to show whether this strategy can be expanded to patients with solid tumors.

Priority focus areas:

Identify and validate novel antigenic targets uniquely present in solid tumors

Explore the safety and activity of promising cellular therapies in solid tumors

Develop strategies that mitigate current challenges in delivering cellular therapies to patients, including ex- ploring the use of cellular products that do not have to be individually manufactured for each patient

Examine and optimize the cancer care delivery sys- tems needed to safely administer cellular therapies to all who might benefit

识别并验证实体瘤中独特存在的新抗原靶标探索对实体瘤可能有效的细胞疗法的安全性和有效性制定策略来减轻当前向患者提供细胞疗法存在的挑战，包括探索通用性的细胞疗法产品，不必为每位患者单独制造检查并优化癌症诊疗服务系统，安全实施细胞疗法


4. 儿童肿瘤的精准医学研究和治疗方法

Increase Precision Medicine Research and Treatment Approaches in Pediatric Cancers

Genomic tools have been widely deployed for adult patients to characterize common mutations across different types of cancer. In certain cancers, the use of these tools has accelerated development of new targeted therapies that have improved and extended patients’ lives. Despite this success in adult patients, precision medicine treatment approaches have yet to be widely integrated into the treatment of pediatric cancers.

Priority focus areas:

Identify genomic or other molecular alterations in pediatric cancers that can serve as potentially ac- tionable treatment targets

Develop effective therapeutic agents thatcan target ge- nomic or other molecularalterations in childhood cancers

Explore the efficacy of existing targeted therapies in pediatric patients with tumors that have mutations shown to be responsive to medicines that work in adult populations

确定儿童肿瘤中可作为潜在治疗目标的基因或其他分子改变针对儿童肿瘤中的基因或其他分子改变，研发有效的靶向治疗药物探索现有靶向治疗药物在儿童患者中的疗效


5. 老年癌症患者的优化照护

Optimize Care for Older Adults With Cancer

Although adults age 65 years and olderrepresent the majority of people with cancer,few cancer clinical trials focus spe- cifically onthis population. Older patients who doparticipate in clinical trials are generally not representative of the older patients whooncologists typically see in daily practice. As a result, clinicians face challenges applyingclinical trial data to older patients who may have additional health conditions, varyinglevels of functional ability, and different goalsfrom clinical trial participants. The lack ofevidence in this area combined with the inherent diversity of aging populations impedes the delivery of high-quality care forthe largest and most rapidly growingsegment of patients with cancer.

Priority focus areas:

Develop standardized methods tocharacterize physio- logic aging, such asgeriatric assessment and biomarkers ofaging, to more reliably predict risk oftreatment-related adverse effects in olderpatients with cancer

Investigate the impact of cancer treatment on physical function, cognition, and quality-of-life to inform toler- ability of cancer therapies in older people

Investigate the efficacy and toxicity of therapies among older adults most under-represented in clinical trials, such as those with impaired functional status, comorbidities, or frailty

Conduct clinical trials testing the role ofgeriatric assessment-guided management toimprove outcomes using personalized care;important focus areas include strategies thatminimize undertreatment of fit patients and overtreatment of vulnerable or frail patients, sup- portive care interventions, and caredelivery interventions

制定老年评估方法和衰老生物标志物，以更可靠预测老年癌症患者治疗相关不良反应的风险调查癌症治疗对身体机能，认知和生活质量的影响，以明确老年人癌症治疗的耐受性调查那些在临床试验中很少被关注的老年人的治疗疗效和毒性，例如功能状态受损、合并其他疾病或虚弱的老年人  


6. 提高癌症患者接受临床试验的机会

Increase Equitable Access to Cancer Clinical Trials

Certain patient populations are consistently under-represented in cancerclinical trials. These include patients fromracial and ethnic minorities, rural areas, and lower socioeconomic groups and patientsolder than age 65 years as well asadolescents and young adults age 15 to 39 years. Decreased representation among thesegroups can limit access to the promisingtreat- ments offered through these trials and means that research findings may not fullyaccount for the diversity of biologic, social, and cultural factors that influence outcomes. Additional re- search is needed to ensurethat every patient with cancer, regardless ofrace, ethnicity, age, geographic location, orso- cioeconomic status, benefits fromresearch advances.

Priority focus areas:

Improve understanding of the barriers to trial enroll- ment among various under-represented groups, taking into consideration patient, practice, community, and trial-specific factors

Develop and test interventions that enhance clinical trial enrollment among under-represented populations (examples may include use of educational tools, tele- health, and community-based involvement and par- ticipatory research)

Evaluate novel strategies to improve access to clinical research resources in areas with large proportions of under-represented minorities

Develop mechanisms that improve awareness and education about clinical trials among under-represented groups and thephysicians treating them

Investigate differences in cancer incidence, preva- lence, natural history of disease, and treatment ex- perience, including efficacy and toxicity, among under-represented populations


7. 降低癌症治疗的长期不良反应

Reduce the Long-Term Consequences of Cancer Treatment

Advances in cancer treatment have resulted in a record number of cancer survivors—more than 15.5 million. Although this is a tremendous accomplishment,survivors still face long-term consequences of cancer, including adverse effects of cancer therapies that affect quality of life. These adverse effects, which commonly include peripheral neuropathy, cognitive impairment, and cardiotoxicity, pose a substantial burden not only to patients but also to the health care system.

Priority  focus areas:

Identify genetic variants associated with increased risk of treatment-related toxicities

Deepen understanding of the underlying mechanisms of toxicities from targeted treatments, determine their contribution to long-term effects, and develop novel strategies to mitigate or eliminate such toxicities

Develop new tools to facilitate long-term tracking of patient outcomes that include patient-reported out- come measures


8. 降低肥胖对癌症发病率和结局的影响

Reduce Obesity’s Impact on Cancer Incidence and Outcomes

The incidence of obesity has dramatically increased over the past several decades. Despite being the second leading preventable cause of cancer, a recent ASCO survey  found that only 35% of Americansrecognize excess body weight as a cancer risk factor. Obesity is associated with poorer cancer survival and can con- tribute to increased risk of treatment-related adverse effects. If current trends continue over the next 20 years, it is estimated that obesity will lead to more than 500,000 additional cases of cancer each year in the United States and will surpass smoking as the leading pre- ventable cause of cancer.

Priority focus areas:

• Improve the understanding of the mechanisms through which weight and energy balance, including physical activity and dietary factors, contribute to cancer development and progression
• Investigate how obesity affects response to therapy, risk of cancer recurrence, andlong-term cancer outcomes
• Assess the impact of energy balance interventions, such as weight loss, increased physical activity, and improved dietary quality, on cancer risk, recurrence, and mortality
• Identify effective interventions that optimize energy bal- ance in people at riskand who are living with cancer
  

9. 癌症病变的诊断和治疗策略

Identify Strategies to Detect and Treat Premalignant Lesions

Many cancers begin as high-risk lesions that invariably progress to invasive cancer. Currently, little is known about the genetic makeup, heterogeneity, microenvironment, and what causes some of these lesions to progress to in- vasive cancer. Increased knowledge will help guide new approaches to intercept and eradicate high-risk lesions before their transformation to malignancy.

Priority focus areas:

• Identify specific molecular pathways that drive pro- gression of preinvasive lesions to invasive cancer and develop interventions that can delay or prevent pro- gression to malignancy
• Identify features of the microenvironment of pre- malignant lesions that are associated with progression to invasive disease
• Investigate novel methods for evaluation of pre- malignant lesions to better inform the risk or likelihood of progression to invasive disease
  

【参考文献】

Sumanta K. Pal, et al. Clinical Cancer Advances 2019: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. jco.org on January 31, 2019: DOI https://doi.org/10.1200/JCO.18.02037  http://ascopubs.org/doi/full/10.1200/JCO.18.02037