Table 1.

The synergy of combination therapies in the market

S.No	Drugs/therapy	Cancer therapy	Targets	Pharmacological action	Limitation	Reference
1.	Doxorubicin	Chemotherapy	Breast cancer, Lung cancer, Hodgkin lymphoma, Non-Hodgkin lymphoma, leukemia, Ovarian cancer, sarcomas	Interacts with DNA	Cardiotoxicity	[227]
				Inhibits topoisomerase
				Disrupts DNA and RNA synthesis	The risk of cumulative toxicity increases with repeated doses, potentially impacting the long-term use of the drug
				Induces cell death
2.	Cisplatin		Testicular, bladder, ovarian, and head-neck cancers	Forms DNA cross-links	Nephrotoxicity	[228, 229]
				Inhibits DNA replication and transcription
					Neurotoxicity
				Promotes cell death
				Causes DNA damage
3.	Paclitaxel and Docetaxel		Breast, ovarian, lung, and prostate cancers	Stabilizes microtubules	Neutropenia (a decrease in white blood cells), increasing the risk of infections	[230, 231]
				Inhibits cell division
				Induces cell death
					Hypersensitivity reactions
4.	Methotrexate		Leukemia, lymphomas, breast, and lung cancers	Inhibits dihydrofolate reductase	Suppress the bone marrow, leading to myelosuppression and an increased risk of infections, anemia, and bleeding	[232]
					High doses of methotrexate can cause renal toxicity
				Disrupts nucleic acid and protein synthesis
				Reduces thymidine production
5.	5-Fluorouracil		Colorectal, breast, stomach, and pancreatic cancers	Inhibits Thymidylate Synthase	Cardiotoxicity	[233]
				Disrupts Thymidine Synthesis	Gastrointestinal toxicity
				Inhibits DNA Synthesis Causes Cell Death
6.	X-ray	Radiation Therapy	Bone Cancer, breast cancer, gastrointestinal cancers, head and neck cancer	They interact with tissues and produce images based on differential absorption	X-rays are non-specific and can affect both cancerous and healthy tissues, leading to potential damage to surrounding normal structures	[234]
7.	Gamma ray		Breast cancer, lung cancer, gastrointestinal cancer, head and neck cancer, brain cancer, prostate cancer, Gynecological Cancers, Bone Metastases	Directed toward damaging DNA in targeted cells	Gamma rays penetrate tissues deeply, they may still cause damage to normal tissues along their path	[235]
8.	Proton ray		Pediatric Cancers, Brain and Spinal Cord Tumors, Eye Tumors (Ocular Melanomas), head and neck cancer, thoracic cancer, Prostate Cancer, Bone and Soft Tissue Sarcomas	Protons deposit their energy in a controlled manner within the targeted tissues, damaging the DNA of cancer cells and inhibiting their ability to divide and grow	Limited accessibility	[236]
9.	Electron beams		Skin cancer, breast cancer, Extremity Sarcomas, head and neck cancer, Keloids and Hypertrophic Scars, Superficial Lymphomas, Eye Tumors	Electron beams interact with tissues to deposit energy. Their use in therapy is aimed at damaging cancer cells and inhibiting their growth	Electron beams are effective for treating superficial tumors but may not penetrate deeply enough for certain deeper-seated tumors	[237]
10.	Curative surgery	Surgery	Breast cancer, colorectal cancer, lung cancer, prostate cancer, thyroid cancer, ovarian cancer, testicular cancer, melanoma, bladder cancer, gastro cancer	Remove the entire tumor or cancerous tissue	Curative surgery may not be feasible if the cancer has spread extensively or if the tumor is located in a critical or inaccessible area	[238]
11.	Debulking surgery		Ovarian, pancreatic, and colorectal cancers	Debulking surgery involves the removal of a portion of the tumor when complete removal is not feasible. The goal is to reduce the size of the tumor, alleviate symptoms, and enhance the effectiveness of other treatments	Debulking surgery may not eliminate all cancer cells, and complete removal may not be achievable in some cases	[239]
12.	Palliative surgery		Palliative surgery used for advanced cancers, easing symptoms, improving comfort	Palliative surgery focuses on alleviating symptoms and improving the quality of life for patients with advanced or incurable cancer. It may involve the removal of a tumor or part of it to reduce pain or obstruction	Palliative surgery does not aim to cure cancer but focuses on symptom relief. It may not be suitable for all patients, especially those with a poor overall health status	[240]
13.	Diagnostic surgery		Cancer biopsy and accurate cancer staging	Diagnostic surgery is performed to obtain a sample of tissue (biopsy) for laboratory analysis, confirming the presence of cancer and determining its characteristics	Diagnostic surgery involves some risk, and there is a possibility of complications. It may not be suitable for all patients, particularly those with significant health issues	[241]
14.	Staging and lymph node removal		Staging surgery used for accurate cancer staging, often involves lymph nodes	Staging surgery helps determine the extent of cancer spread, and it often involves the removal and examination of nearby lymph nodes to assess whether the cancer has spread	Staging surgery may not detect microscopic metastases, and the removal of lymph nodes may cause complications such as lymphedema	[242]
15.	Reconstructive surgery		Breast cancer	Reconstructive surgery is performed to restore the appearance or function of an area after cancer removal	Reconstructive surgery may have aesthetic and functional limitations, and it may not be suitable for all patients, especially those with certain health conditions	[243]
16.	Minimally invasive surgery		Gastrointestinal Cancers, Gynecological Cancers, Thoracic cancer, prostate cancer, head and neck cancer, kidney cancer, liver cancer, and pancreatic cancer	Minimally invasive surgery uses small incisions and specialized instruments to perform procedures with less impact on surrounding tissues	Minimally invasive surgery may not be suitable for complex or extensive procedures, and it may have a steeper learning curve for surgeons	[244]